Professor Ian Humphreys
Professor of Viral Pathogenesis and Lead Co-Director of Systems Immunity Research Institute
Overview
I am a Professor of Viral Pathogenesis and Wellcome Trust Senior Research Fellow in Basic Biomedical Sciences within the Division of Infection & Immunity, School of Medicine. My laboratory studies the regulation of immune responses during viral infections. I am also Lead Co-Director of the Systems Immunity University Research Institute and Lead for Infections and Pandemics.
Publication
2024
- Al-Talib, M., Dimonte, S. and Humphreys, I. R. 2024. Mucosal T-cell responses to chronic viral infections: Implications for vaccine design. Cellular & Molecular Immunology 21, pp. 982-998. (10.1038/s41423-024-01140-2)
- Bliss, C. M. et al. 2024. A pseudotyped adenovirus serotype 5 vector with serotype 49 fiber knob is an effective vector for vaccine and gene therapy applications. Molecular Therapy - Methods and Clinical Development 32(3), article number: 101308. (10.1016/j.omtm.2024.101308)
- Amratia, P. S., Kerr-Jones, L. E., Chapman, L., Marsden, M., Clement, M., Stanton, R. J. and Humphreys, I. R. 2024. Cytomegalovirus-induced peroxynitrite promotes virus entry and contributes to pathogenesis in a murine model of infection. mBio 15(8), article number: e03152-23. (10.1128/mbio.03152-23)
- Hulin-Curtis, S. et al. 2024. A targeted single mutation in influenza A virus universal epitope transforms immunogenicity and protective immunity via CD4+ T cell activation. Cell Reports 43(6), article number: 114259. (10.1016/j.celrep.2024.114259)
2023
- Whiteside, S. K. et al. 2023. Acquisition of suppressive function by conventional T cells limits antitumor immunity upon Treg depletion. Science Immunology 8(90), article number: eabo5558. (10.1126/sciimmunol.abo5558)
- Clement, M. et al. 2023. Inhibitory IL-10-producing CD4+ T cells are T-bet-dependent and facilitate cytomegalovirus persistence via coexpression of arginase-1. eLife 12, article number: e79165. (10.7554/eLife.79165)
2022
- Jessop, Z. M. et al. 2022. A study protocol for a double-blind randomised placebo-controlled trial evaluating the efficacy of carrageenan nasal and throat spray for COVID-19 prophylaxis—ICE-COVID. Trials 23(1), article number: 782. (10.1186/s13063-022-06685-z)
- Clement, M. et al. 2022. IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses. Nature Communications 13(1), article number: 5294. (10.1038/s41467-022-32587-4)
- Asderakis, A. et al. 2022. An analysis of serological response and infection outcomes following Oxford-AstraZeneca (AZD1222) and Pfizer-BioNTech (mRNA BNT162b2) SARS-CoV-2 vaccines in kidney and kidney pancreas transplants. Transplantation 106(7), pp. 1421-1429. (10.1097/tp.0000000000004105)
- Saud, Z. et al. 2022. Mechanically ventilated patients shed high titre live SARS-CoV2 for extended periods from both the upper and lower respiratory tract. Clinical Infectious Diseases 75(1), pp. e82-e88., article number: ciac170. (10.1093/cid/ciac170)
- Fielding, C. A. et al. 2022. SARS-CoV-2 host-shutoff impacts innate NK cell functions, but antibody-dependent NK activity is strongly activated through non-spike antibodies. eLife 11 (10.7554/eLife.74489)
- Ponsford, M. J. et al. 2022. Examining the utility of extended laboratory panel testing in the emergency department for risk stratification of patients with COVID-19: a single-centre retrospective service evaluation. Journal of Clinical Pathology 75(4), pp. 255-262. (10.1136/jclinpath-2020-207157)
2021
- Ponsford, M. J. et al. 2021. Burden of nosocomial COVID-19 in Wales: results from a multicentre retrospective observational study of 2508 hospitalised adults. Thorax 76(12), pp. 1246-1249. (10.1136/thoraxjnl-2021-216964)
- Dimonte, S., Gimeno-Brias, S., Marsden, M., Chapman, L., Sabberwal, P., Clement, M. and Humphreys, I. R. 2021. Optimal CD8+ T-cell memory formation following subcutaneous cytomegalovirus infection requires virus replication but not early dendritic cell responses. Immunology 164(2), pp. 279-291. (10.1111/imm.13368)
- Ponsford, M. J. et al. 2021. A systematic review and meta-analysis of inpatient mortality associated with nosocomial and community COVID-19 exposes the vulnerability of immunosuppressed adults. Frontiers in Immunology 12, article number: 744696. (10.3389/fimmu.2021.744696)
- Ponsford, M. J., Shillitoe, B. M., Humphreys, I. R., Gennery, A. R. and Jolles, S. 2021. COVID-19 and X-linked agammaglobulinemia (XLA) - insights from a monogenic antibody deficiency. Current Opinion in Allergy and Clinical Immunology (10.1097/ACI.0000000000000792)
- Humphreys, I. R. and Godkin, A. J. 2021. Reply to a scientific basis for anxiety about the emergence of resistant strains of Covid-19. QJM: An International Journal of Medicine 114(7) (10.1093/qjmed/hcab056)
- Clement, M. et al. 2021. IFITM3 regulates virus-induced inflammatory cytokine production by titrating Nogo-B orchestration of TLR responses. [Online]. bioRxiv. Available at: https://doi.org/10.1101/2021.07.23.453513
- Wellington, D. et al. 2021. IFITM3‐specific antibody reveals IFN preferences and slow IFN induction of the antiviral factor IFITM3 in humans. European Journal of Immunology 51(3), pp. 742-745. (10.1002/eji.202048706)
- Forbester, J. L. and Humphreys, I. R. 2021. Genetic influences on viral-induced cytokine responses in the lung. Mucosal Immunology 14, pp. 14-25. (10.1038/s41385-020-00355-6)
2020
- Lucchesi, D. et al. 2020. Impaired IL‐27 mediated control of CD4+ T cell function impacts on ectopic lymphoid structure formation in patients with Sjögren's Syndrome. Arthritis and Rheumatology 72(9), pp. 1559-1570., article number: Volume72, Issue9 September 2020 Pages 1559-1570. (10.1002/art.41289)
- Godkin, A. and Humphreys, I. R. 2020. Elevated interleukin‐6, interleukin‐10 and neutrophil : lymphocyte ratio as identifiers of severe coronavirus disease 2019 [Editorial]. Immunology 160(3), pp. 221-222. (10.1111/imm.13225)
- O'Donnell, V. B. et al. 2020. Potential role of oral rinses targeting the viral lipid envelope in SARS-CoV-2 infection. Function 1(1), article number: zqaa002. (10.1093/function/zqaa002)
- De Trez, C. et al. 2020. A critical Blimp-1-dependent IL-10 regulatory pathway in T cells protects from a lethal pro-inflammatory cytokine storm during acute experimental Trypanosoma brucei Infection. Frontiers in Immunology 11, article number: 1085. (10.3389/fimmu.2020.01085)
- Forbester, J. L. et al. 2020. IRF5 promotes influenza-induced inflammatory responses in human iPSC-derived myeloid cells and murine models. Journal of Virology 94(9), article number: e00121-20. (10.1128/JVI.00121-20)
2019
- Shelkovnikova, T. A., An, H., Skelt, L., Tregoning, J. S., Humphreys, I. R. and Buchman, V. L. 2019. Antiviral immune response as a trigger of FUS proteinopathy in amyotrophic lateral sclerosis. Cell Reports 29(13), pp. 4496-4508.e4. (10.1016/j.celrep.2019.11.094)
- Singhania, A. et al. 2019. Transcriptional profiling unveils type I and II interferon networks in blood and tissues across diseases. Nature Communications 10, article number: 2887. (10.1038/s41467-019-10601-6)
- Thompson, A. et al. 2019. The protective effect of inflammatory monocytes during systemic C. albicans infection is dependent on collaboration between C-type lectin-like receptors. PLoS Pathogens 15(6), article number: e1007850. (10.1371/journal.ppat.1007850)
- Smith, S. E. et al. 2019. Interferon-induced Transmembrane Protein 1 restricts replication of virus that enter cells via the plasma membrane.. Journal of Virology 93(6), article number: e02003-18. (10.1128/JVI.02003-18)
- McLaren, J. et al. 2019. IL-33 augments virus-specific memory T Cell inflation and potentiates the efficacy of an attenuated cytomegalovirus-based vaccinea. Journal of Immunology 202(3), pp. 943-955. (10.4049/jimmunol.1701757)
- Clement, M. and Humphreys, I. R. 2019. Cytokine-mediated induction and regulation of tissue damage during cytomegalovirus infection. Frontiers in Immunology 10, article number: 78. (10.3389/fimmu.2019.00078)
2018
- Gimeno Brias, S. et al. 2018. Interferon lambda is required for interferon gamma-expressing NK cell responses but does not afford antiviral protection during acute and persistent murine cytomegalovirus infection. PLoS ONE 13(5), article number: e0197596. (10.1371/journal.pone.0197596)
- Humphreys, I. R. and Sebastian, S. 2018. Novel viral vectors in infectious diseases. Immunology 153(1), pp. 1-9. (10.1111/imm.12829)
2017
- Rai, T. S. et al. 2017. Histone chaperone HIRA deposits histone H3.3 onto foreign viral DNA and contributes to anti-viral intrinsic immunity. Nucleic Acids Research 45(20), pp. 11673-11683. (10.1093/nar/gkx771)
- Sowerby, J. M. et al. 2017. NBEAL2 is required for neutrophil and NK cell function and pathogen defense. Journal of Clinical Investigation 127(9), pp. 3521-3526. (10.1172/JCI91684)
- Stacey, M. A. et al. 2017. The antiviral restriction factor IFN-induced transmembrane protein 3 prevents cytokine-driven CMV pathogenesis. Journal of Clinical Investigation 127(4), pp. 1463-1474. (10.1172/JCI84889)
2016
- Clement, M. et al. 2016. Cytomegalovirus-specific IL-10-producing CD4+ T cells are governed by type-I IFN-induced IL-27 and promote virus persistence. Plos Pathogens 12(12), article number: e1006050. (10.1371/journal.ppat.1006050)
- Perks, W. V. et al. 2016. Death Receptor 3 promotes chemokine directed leukocyte recruitment in acute resolving inflammation and is essential for pathological development of mesothelial fibrosis in chronic disease. American Journal of Pathology 186(11), pp. 2813-2823. (10.1016/j.ajpath.2016.07.021)
- Liao, C. et al. 2016. IL-10 differentially controls the infiltration of inflammatory macrophages and antigen-presenting cells during inflammation. European Journal of Immunology 46(9), pp. 2222-2232. (10.1002/eji.201646528)
- Patin, E. et al. 2016. IL-27 induced by Select Candida spp. via TLR7/NOD2 signaling and IFN-β production inhibits fungal clearance. The Journal of Immunology 197(1), pp. 208-221. (10.4049/jimmunol.1501204)
- Gimeno Brias, S., Stack, G., Stacey, M. A., Redwood, A. J. and Humphreys, I. R. 2016. The role of IL-22 in viral infections: paradigms and paradoxes. Frontiers in Immunology 7, article number: 211. (10.3389/fimmu.2016.00211)
- Mohammed, R. N., Watson, H. A., Vigar, M., Ohme, J., Thomson, A., Humphreys, I. R. and Ager, A. 2016. L-selectin is essential for delivery of activated CD8+ T cells to virus-infected organs for protective immunity. Cell Reports 14(4), pp. 760-771. (10.1016/j.celrep.2015.12.090)
2015
- Stack, G. et al. 2015. CD200 receptor restriction of myeloid cell responses antagonizes antiviral immunity and facilitates cytomegalovirus persistence within mucosal tissue. PLoS Pathogens 11(2), article number: e1004641. (10.1371/journal.ppat.1004641)
2014
- Greenhill, C. J. et al. 2014. Interleukin-10 regulates the inflammasome-driven augmentation of inflammatory arthritis and joint destruction. Arthritis Research and Therapy 16(4), article number: 419. (10.1186/s13075-014-0419-y)
- Stacey, M. A. et al. 2014. Neutrophils recruited by IL-22 in peripheral tissues function as TRAIL-dependent antiviral effectors against MCMV. Cell Host and Microbe 15(4), pp. 471-483. (10.1016/j.chom.2014.03.003)
- Fielding, C. A. et al. 2014. Interleukin-6 signaling drives fibrosis in unresolved inflammation. Immunity 40(1), pp. 40-50. (10.1016/j.immuni.2013.10.022)
- Segrott, J. et al. 2014. Fidelity of implementation of the Strengthening Families Programme 10-14 UK in Wales UK: a mixed-method process evaluation within a randomised controlled trial. Presented at: 7th European Public Health Conference, Glasgow, Scotland,, 19-22 November 2014.
2013
- Greenhill, C. J. et al. 2013. Interleukin 10 control of the inflammasome restricts arthritic bone erosion [Abstract]. Cytokine 63(3), pp. 267. (10.1016/j.cyto.2013.06.105)
2012
- Humphreys, I. R. et al. 2012. Avidity of influenza-specific memory CD8+T-cell populations decays over time compromising antiviral immunity. European Journal of Immunology 42(12), pp. 3235-3242. (10.1002/eji.201242575)
- Greenhill, C. J. et al. 2012. Cross-talk between IL-10 and the inflammasome regulates bone erosions during rheumatoid arthritis [Abstract]. Immunology 137, pp. 43-44.
- Pembroke, T. et al. 2012. Rapid early innate control of hepatitis C virus during IFN-α treatment compromises adaptive CD4+T-cell immunity. European Journal of Immunology 42(9), pp. 2383-2394. (10.1002/eji.201142072)
- Twohig, J. P. et al. 2012. The death receptor 3/TL1A pathway is essential for efficient development of antiviral CD4+ and CD8+ T-cell immunity. The FASEB Journal 26(8), pp. 3575-3586. (10.1096/fj.11-200618)
- Stack, G., Stacey, M. A. and Humphreys, I. R. 2012. Herpesvirus exploitation of host immune inhibitory pathways. Viruses 4(12), pp. 1182-1201. (10.3390/v4081182)
- Greenhill, C. et al. 2012. The regulation of arthritic bone erosions by il-10 [Abstract]. Rhuematology 51, pp. 48-48. (10.1093/rheumatology/kes117)
2011
- Greenhill, C. J. et al. 2011. The regulation of arthritic bone erosions by IL-10 [Abstract]. Immunology 135(s1), pp. 158-158. (10.1111/j.1365-2567.2011.03534.x)
- Stacey, M. A., Marsden, M., Wang, E. C. Y., Wilkinson, G. W. G. and Humphreys, I. R. 2011. IL-10 restricts activation-induced death of NK cells during acute murine cytomegalovirus infection. The Journal of Immunology 187(6), pp. 2944-2952. (10.4049/jimmunol.1101021)
2010
- Humphreys, I. R. et al. 2010. Biphasic role of 4-1BB in the regulation of mouse cytomegalovirus-specific CD8+ T cells. European Journal of Immunology 40(10), pp. 2762-2768. (10.1002/eji.200940256)
- Jones, M. et al. 2010. IL-10 restricts memory T cell inflation during cytomegalovirus infection. The Journal of Immunology 185(6), pp. 3583-3592. (10.4049/jimmunol.1001535)
2007
- Humphreys, I. R. et al. 2007. OX40 costimulation promotes persistence of cytomegalovirus-specific CD8 T cells: a CD4 dependent mechanism. Journal of Immunology 179, pp. 2195-2202.
- Humphreys, I. R., De Trez, C., Kinkade, A., Benedict, C. A., Croft, M. and Ware, C. F. 2007. Cytomegalovirus exploits IL-10-mediated immune regulation in the salivary glands. Journal of Experimental Medicine 204(5), pp. 1217-25. (10.1084/jem.20062424)
2005
- Cheung, T. C. et al. 2005. Evolutionarily divergent herpesviruses modulate T cell activation by targeting the herpesvirus entry mediator cosignaling pathway. Proceedings of the National Academy of Sciences 102(47), pp. 13218-13223. (10.1073/pnas.0506172102)
- Stewart, G. R. et al. 2005. The stress-responsive chaperone alpha-crystallin 2 is required for pathogenesis of Mycobacterium tuberculosis. Molecular Microbiology 55(4), pp. 1127-1137. (10.1111/j.1365-2958.2004.04450.x)
2004
- Hale, C. et al. 2004. Mucosal immunisation of murine neonates using whole cell and acellular Pertussis vaccines. Vaccine 22(27-28), pp. 3595-3602. (10.1016/j.vaccine.2004.03.039)
- Hussell, T., Snelgrove, R., Humphreys, I. and Williams, A. E. 2004. Co-stimulation: novel methods for preventing viral-induced lung inflammation. Trends in Molecular Medicine 10(8), pp. 379-386. (10.1016/j.molmed.2004.06.006)
2003
- Humphreys, I. R., Walzl, G., Hussell, T. and Hill, S. 2003. A critical role for OX40 in T cell-mediated immunopathology during lung viral infection. Journal of Experimental Medicine 198(8), pp. 1237-42. (10.1084/jem.20030351)
- Humphreys, I., Edwards, L. C., Walzl, G., Rae, A. J., Dougan, G., Hill, S. and Hussell, T. 2003. OX40 ligation on activated T cells enhances the control of Cryptococcus neoformans and reduces pulmonary eosinophilia. Journal of Immunology 170(12), pp. 6125-6132. (10.4049/jimmunol.170.12.6125)
- Walzl, G., Humphreys, I., Marshall, B. G., Edwards, L. C., Openshaw, P. J., Shaw, R. J. and Hussell, T. 2003. Prior exposure to live Mycobacterium bovis BCG decreases Cryptococcus neoformans-induced lung eosinophilia in a gamma interferon-dependent manner. Infection and Immunity 71(6), pp. 3384-3391. (10.1128/IAI.71.6.3384-3391.2003)
2002
- Dearman, R., Filby, A., Humphreys, I. and Kimber, I. 2002. Interleukins 5 and 13 characterize immune responses to respiratory sensitizing acid anhydrides. Journal of Applied Toxicology 22(5), pp. 317-325. (10.1002/jat.865)
2000
- Dearman, R., Warbrick, E., Humphreys, I. and Kimber, I. 2000. Characterization in mice of the immunological properties of five allergenic acid anhydrides. Journal of Applied Toxicology 20(3), pp. 221-230. (10.1002/(SICI)1099-1263(200005/06)20:3<221::AID-JAT651>3.0.CO;2-#)
Articles
- Al-Talib, M., Dimonte, S. and Humphreys, I. R. 2024. Mucosal T-cell responses to chronic viral infections: Implications for vaccine design. Cellular & Molecular Immunology 21, pp. 982-998. (10.1038/s41423-024-01140-2)
- Bliss, C. M. et al. 2024. A pseudotyped adenovirus serotype 5 vector with serotype 49 fiber knob is an effective vector for vaccine and gene therapy applications. Molecular Therapy - Methods and Clinical Development 32(3), article number: 101308. (10.1016/j.omtm.2024.101308)
- Amratia, P. S., Kerr-Jones, L. E., Chapman, L., Marsden, M., Clement, M., Stanton, R. J. and Humphreys, I. R. 2024. Cytomegalovirus-induced peroxynitrite promotes virus entry and contributes to pathogenesis in a murine model of infection. mBio 15(8), article number: e03152-23. (10.1128/mbio.03152-23)
- Hulin-Curtis, S. et al. 2024. A targeted single mutation in influenza A virus universal epitope transforms immunogenicity and protective immunity via CD4+ T cell activation. Cell Reports 43(6), article number: 114259. (10.1016/j.celrep.2024.114259)
- Whiteside, S. K. et al. 2023. Acquisition of suppressive function by conventional T cells limits antitumor immunity upon Treg depletion. Science Immunology 8(90), article number: eabo5558. (10.1126/sciimmunol.abo5558)
- Clement, M. et al. 2023. Inhibitory IL-10-producing CD4+ T cells are T-bet-dependent and facilitate cytomegalovirus persistence via coexpression of arginase-1. eLife 12, article number: e79165. (10.7554/eLife.79165)
- Jessop, Z. M. et al. 2022. A study protocol for a double-blind randomised placebo-controlled trial evaluating the efficacy of carrageenan nasal and throat spray for COVID-19 prophylaxis—ICE-COVID. Trials 23(1), article number: 782. (10.1186/s13063-022-06685-z)
- Clement, M. et al. 2022. IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses. Nature Communications 13(1), article number: 5294. (10.1038/s41467-022-32587-4)
- Asderakis, A. et al. 2022. An analysis of serological response and infection outcomes following Oxford-AstraZeneca (AZD1222) and Pfizer-BioNTech (mRNA BNT162b2) SARS-CoV-2 vaccines in kidney and kidney pancreas transplants. Transplantation 106(7), pp. 1421-1429. (10.1097/tp.0000000000004105)
- Saud, Z. et al. 2022. Mechanically ventilated patients shed high titre live SARS-CoV2 for extended periods from both the upper and lower respiratory tract. Clinical Infectious Diseases 75(1), pp. e82-e88., article number: ciac170. (10.1093/cid/ciac170)
- Fielding, C. A. et al. 2022. SARS-CoV-2 host-shutoff impacts innate NK cell functions, but antibody-dependent NK activity is strongly activated through non-spike antibodies. eLife 11 (10.7554/eLife.74489)
- Ponsford, M. J. et al. 2022. Examining the utility of extended laboratory panel testing in the emergency department for risk stratification of patients with COVID-19: a single-centre retrospective service evaluation. Journal of Clinical Pathology 75(4), pp. 255-262. (10.1136/jclinpath-2020-207157)
- Ponsford, M. J. et al. 2021. Burden of nosocomial COVID-19 in Wales: results from a multicentre retrospective observational study of 2508 hospitalised adults. Thorax 76(12), pp. 1246-1249. (10.1136/thoraxjnl-2021-216964)
- Dimonte, S., Gimeno-Brias, S., Marsden, M., Chapman, L., Sabberwal, P., Clement, M. and Humphreys, I. R. 2021. Optimal CD8+ T-cell memory formation following subcutaneous cytomegalovirus infection requires virus replication but not early dendritic cell responses. Immunology 164(2), pp. 279-291. (10.1111/imm.13368)
- Ponsford, M. J. et al. 2021. A systematic review and meta-analysis of inpatient mortality associated with nosocomial and community COVID-19 exposes the vulnerability of immunosuppressed adults. Frontiers in Immunology 12, article number: 744696. (10.3389/fimmu.2021.744696)
- Ponsford, M. J., Shillitoe, B. M., Humphreys, I. R., Gennery, A. R. and Jolles, S. 2021. COVID-19 and X-linked agammaglobulinemia (XLA) - insights from a monogenic antibody deficiency. Current Opinion in Allergy and Clinical Immunology (10.1097/ACI.0000000000000792)
- Humphreys, I. R. and Godkin, A. J. 2021. Reply to a scientific basis for anxiety about the emergence of resistant strains of Covid-19. QJM: An International Journal of Medicine 114(7) (10.1093/qjmed/hcab056)
- Wellington, D. et al. 2021. IFITM3‐specific antibody reveals IFN preferences and slow IFN induction of the antiviral factor IFITM3 in humans. European Journal of Immunology 51(3), pp. 742-745. (10.1002/eji.202048706)
- Forbester, J. L. and Humphreys, I. R. 2021. Genetic influences on viral-induced cytokine responses in the lung. Mucosal Immunology 14, pp. 14-25. (10.1038/s41385-020-00355-6)
- Lucchesi, D. et al. 2020. Impaired IL‐27 mediated control of CD4+ T cell function impacts on ectopic lymphoid structure formation in patients with Sjögren's Syndrome. Arthritis and Rheumatology 72(9), pp. 1559-1570., article number: Volume72, Issue9 September 2020 Pages 1559-1570. (10.1002/art.41289)
- Godkin, A. and Humphreys, I. R. 2020. Elevated interleukin‐6, interleukin‐10 and neutrophil : lymphocyte ratio as identifiers of severe coronavirus disease 2019 [Editorial]. Immunology 160(3), pp. 221-222. (10.1111/imm.13225)
- O'Donnell, V. B. et al. 2020. Potential role of oral rinses targeting the viral lipid envelope in SARS-CoV-2 infection. Function 1(1), article number: zqaa002. (10.1093/function/zqaa002)
- De Trez, C. et al. 2020. A critical Blimp-1-dependent IL-10 regulatory pathway in T cells protects from a lethal pro-inflammatory cytokine storm during acute experimental Trypanosoma brucei Infection. Frontiers in Immunology 11, article number: 1085. (10.3389/fimmu.2020.01085)
- Forbester, J. L. et al. 2020. IRF5 promotes influenza-induced inflammatory responses in human iPSC-derived myeloid cells and murine models. Journal of Virology 94(9), article number: e00121-20. (10.1128/JVI.00121-20)
- Shelkovnikova, T. A., An, H., Skelt, L., Tregoning, J. S., Humphreys, I. R. and Buchman, V. L. 2019. Antiviral immune response as a trigger of FUS proteinopathy in amyotrophic lateral sclerosis. Cell Reports 29(13), pp. 4496-4508.e4. (10.1016/j.celrep.2019.11.094)
- Singhania, A. et al. 2019. Transcriptional profiling unveils type I and II interferon networks in blood and tissues across diseases. Nature Communications 10, article number: 2887. (10.1038/s41467-019-10601-6)
- Thompson, A. et al. 2019. The protective effect of inflammatory monocytes during systemic C. albicans infection is dependent on collaboration between C-type lectin-like receptors. PLoS Pathogens 15(6), article number: e1007850. (10.1371/journal.ppat.1007850)
- Smith, S. E. et al. 2019. Interferon-induced Transmembrane Protein 1 restricts replication of virus that enter cells via the plasma membrane.. Journal of Virology 93(6), article number: e02003-18. (10.1128/JVI.02003-18)
- McLaren, J. et al. 2019. IL-33 augments virus-specific memory T Cell inflation and potentiates the efficacy of an attenuated cytomegalovirus-based vaccinea. Journal of Immunology 202(3), pp. 943-955. (10.4049/jimmunol.1701757)
- Clement, M. and Humphreys, I. R. 2019. Cytokine-mediated induction and regulation of tissue damage during cytomegalovirus infection. Frontiers in Immunology 10, article number: 78. (10.3389/fimmu.2019.00078)
- Gimeno Brias, S. et al. 2018. Interferon lambda is required for interferon gamma-expressing NK cell responses but does not afford antiviral protection during acute and persistent murine cytomegalovirus infection. PLoS ONE 13(5), article number: e0197596. (10.1371/journal.pone.0197596)
- Humphreys, I. R. and Sebastian, S. 2018. Novel viral vectors in infectious diseases. Immunology 153(1), pp. 1-9. (10.1111/imm.12829)
- Rai, T. S. et al. 2017. Histone chaperone HIRA deposits histone H3.3 onto foreign viral DNA and contributes to anti-viral intrinsic immunity. Nucleic Acids Research 45(20), pp. 11673-11683. (10.1093/nar/gkx771)
- Sowerby, J. M. et al. 2017. NBEAL2 is required for neutrophil and NK cell function and pathogen defense. Journal of Clinical Investigation 127(9), pp. 3521-3526. (10.1172/JCI91684)
- Stacey, M. A. et al. 2017. The antiviral restriction factor IFN-induced transmembrane protein 3 prevents cytokine-driven CMV pathogenesis. Journal of Clinical Investigation 127(4), pp. 1463-1474. (10.1172/JCI84889)
- Clement, M. et al. 2016. Cytomegalovirus-specific IL-10-producing CD4+ T cells are governed by type-I IFN-induced IL-27 and promote virus persistence. Plos Pathogens 12(12), article number: e1006050. (10.1371/journal.ppat.1006050)
- Perks, W. V. et al. 2016. Death Receptor 3 promotes chemokine directed leukocyte recruitment in acute resolving inflammation and is essential for pathological development of mesothelial fibrosis in chronic disease. American Journal of Pathology 186(11), pp. 2813-2823. (10.1016/j.ajpath.2016.07.021)
- Liao, C. et al. 2016. IL-10 differentially controls the infiltration of inflammatory macrophages and antigen-presenting cells during inflammation. European Journal of Immunology 46(9), pp. 2222-2232. (10.1002/eji.201646528)
- Patin, E. et al. 2016. IL-27 induced by Select Candida spp. via TLR7/NOD2 signaling and IFN-β production inhibits fungal clearance. The Journal of Immunology 197(1), pp. 208-221. (10.4049/jimmunol.1501204)
- Gimeno Brias, S., Stack, G., Stacey, M. A., Redwood, A. J. and Humphreys, I. R. 2016. The role of IL-22 in viral infections: paradigms and paradoxes. Frontiers in Immunology 7, article number: 211. (10.3389/fimmu.2016.00211)
- Mohammed, R. N., Watson, H. A., Vigar, M., Ohme, J., Thomson, A., Humphreys, I. R. and Ager, A. 2016. L-selectin is essential for delivery of activated CD8+ T cells to virus-infected organs for protective immunity. Cell Reports 14(4), pp. 760-771. (10.1016/j.celrep.2015.12.090)
- Stack, G. et al. 2015. CD200 receptor restriction of myeloid cell responses antagonizes antiviral immunity and facilitates cytomegalovirus persistence within mucosal tissue. PLoS Pathogens 11(2), article number: e1004641. (10.1371/journal.ppat.1004641)
- Greenhill, C. J. et al. 2014. Interleukin-10 regulates the inflammasome-driven augmentation of inflammatory arthritis and joint destruction. Arthritis Research and Therapy 16(4), article number: 419. (10.1186/s13075-014-0419-y)
- Stacey, M. A. et al. 2014. Neutrophils recruited by IL-22 in peripheral tissues function as TRAIL-dependent antiviral effectors against MCMV. Cell Host and Microbe 15(4), pp. 471-483. (10.1016/j.chom.2014.03.003)
- Fielding, C. A. et al. 2014. Interleukin-6 signaling drives fibrosis in unresolved inflammation. Immunity 40(1), pp. 40-50. (10.1016/j.immuni.2013.10.022)
- Greenhill, C. J. et al. 2013. Interleukin 10 control of the inflammasome restricts arthritic bone erosion [Abstract]. Cytokine 63(3), pp. 267. (10.1016/j.cyto.2013.06.105)
- Humphreys, I. R. et al. 2012. Avidity of influenza-specific memory CD8+T-cell populations decays over time compromising antiviral immunity. European Journal of Immunology 42(12), pp. 3235-3242. (10.1002/eji.201242575)
- Greenhill, C. J. et al. 2012. Cross-talk between IL-10 and the inflammasome regulates bone erosions during rheumatoid arthritis [Abstract]. Immunology 137, pp. 43-44.
- Pembroke, T. et al. 2012. Rapid early innate control of hepatitis C virus during IFN-α treatment compromises adaptive CD4+T-cell immunity. European Journal of Immunology 42(9), pp. 2383-2394. (10.1002/eji.201142072)
- Twohig, J. P. et al. 2012. The death receptor 3/TL1A pathway is essential for efficient development of antiviral CD4+ and CD8+ T-cell immunity. The FASEB Journal 26(8), pp. 3575-3586. (10.1096/fj.11-200618)
- Stack, G., Stacey, M. A. and Humphreys, I. R. 2012. Herpesvirus exploitation of host immune inhibitory pathways. Viruses 4(12), pp. 1182-1201. (10.3390/v4081182)
- Greenhill, C. et al. 2012. The regulation of arthritic bone erosions by il-10 [Abstract]. Rhuematology 51, pp. 48-48. (10.1093/rheumatology/kes117)
- Greenhill, C. J. et al. 2011. The regulation of arthritic bone erosions by IL-10 [Abstract]. Immunology 135(s1), pp. 158-158. (10.1111/j.1365-2567.2011.03534.x)
- Stacey, M. A., Marsden, M., Wang, E. C. Y., Wilkinson, G. W. G. and Humphreys, I. R. 2011. IL-10 restricts activation-induced death of NK cells during acute murine cytomegalovirus infection. The Journal of Immunology 187(6), pp. 2944-2952. (10.4049/jimmunol.1101021)
- Humphreys, I. R. et al. 2010. Biphasic role of 4-1BB in the regulation of mouse cytomegalovirus-specific CD8+ T cells. European Journal of Immunology 40(10), pp. 2762-2768. (10.1002/eji.200940256)
- Jones, M. et al. 2010. IL-10 restricts memory T cell inflation during cytomegalovirus infection. The Journal of Immunology 185(6), pp. 3583-3592. (10.4049/jimmunol.1001535)
- Humphreys, I. R. et al. 2007. OX40 costimulation promotes persistence of cytomegalovirus-specific CD8 T cells: a CD4 dependent mechanism. Journal of Immunology 179, pp. 2195-2202.
- Humphreys, I. R., De Trez, C., Kinkade, A., Benedict, C. A., Croft, M. and Ware, C. F. 2007. Cytomegalovirus exploits IL-10-mediated immune regulation in the salivary glands. Journal of Experimental Medicine 204(5), pp. 1217-25. (10.1084/jem.20062424)
- Cheung, T. C. et al. 2005. Evolutionarily divergent herpesviruses modulate T cell activation by targeting the herpesvirus entry mediator cosignaling pathway. Proceedings of the National Academy of Sciences 102(47), pp. 13218-13223. (10.1073/pnas.0506172102)
- Stewart, G. R. et al. 2005. The stress-responsive chaperone alpha-crystallin 2 is required for pathogenesis of Mycobacterium tuberculosis. Molecular Microbiology 55(4), pp. 1127-1137. (10.1111/j.1365-2958.2004.04450.x)
- Hale, C. et al. 2004. Mucosal immunisation of murine neonates using whole cell and acellular Pertussis vaccines. Vaccine 22(27-28), pp. 3595-3602. (10.1016/j.vaccine.2004.03.039)
- Hussell, T., Snelgrove, R., Humphreys, I. and Williams, A. E. 2004. Co-stimulation: novel methods for preventing viral-induced lung inflammation. Trends in Molecular Medicine 10(8), pp. 379-386. (10.1016/j.molmed.2004.06.006)
- Humphreys, I. R., Walzl, G., Hussell, T. and Hill, S. 2003. A critical role for OX40 in T cell-mediated immunopathology during lung viral infection. Journal of Experimental Medicine 198(8), pp. 1237-42. (10.1084/jem.20030351)
- Humphreys, I., Edwards, L. C., Walzl, G., Rae, A. J., Dougan, G., Hill, S. and Hussell, T. 2003. OX40 ligation on activated T cells enhances the control of Cryptococcus neoformans and reduces pulmonary eosinophilia. Journal of Immunology 170(12), pp. 6125-6132. (10.4049/jimmunol.170.12.6125)
- Walzl, G., Humphreys, I., Marshall, B. G., Edwards, L. C., Openshaw, P. J., Shaw, R. J. and Hussell, T. 2003. Prior exposure to live Mycobacterium bovis BCG decreases Cryptococcus neoformans-induced lung eosinophilia in a gamma interferon-dependent manner. Infection and Immunity 71(6), pp. 3384-3391. (10.1128/IAI.71.6.3384-3391.2003)
- Dearman, R., Filby, A., Humphreys, I. and Kimber, I. 2002. Interleukins 5 and 13 characterize immune responses to respiratory sensitizing acid anhydrides. Journal of Applied Toxicology 22(5), pp. 317-325. (10.1002/jat.865)
- Dearman, R., Warbrick, E., Humphreys, I. and Kimber, I. 2000. Characterization in mice of the immunological properties of five allergenic acid anhydrides. Journal of Applied Toxicology 20(3), pp. 221-230. (10.1002/(SICI)1099-1263(200005/06)20:3<221::AID-JAT651>3.0.CO;2-#)
Conferences
- Segrott, J. et al. 2014. Fidelity of implementation of the Strengthening Families Programme 10-14 UK in Wales UK: a mixed-method process evaluation within a randomised controlled trial. Presented at: 7th European Public Health Conference, Glasgow, Scotland,, 19-22 November 2014.
Websites
- Clement, M. et al. 2021. IFITM3 regulates virus-induced inflammatory cytokine production by titrating Nogo-B orchestration of TLR responses. [Online]. bioRxiv. Available at: https://doi.org/10.1101/2021.07.23.453513
- Segrott, J. et al. 2014. Fidelity of implementation of the Strengthening Families Programme 10-14 UK in Wales UK: a mixed-method process evaluation within a randomised controlled trial. Presented at: 7th European Public Health Conference, Glasgow, Scotland,, 19-22 November 2014.
Research
Our laboratory uses in vivo models of viral infection in combination with clinical samples to help us understand the mechanisms that regulate antiviral immunity.
Immune mechanisms that facilitate virus persistence:
Herpesviruses including the beta-herpesvirus human cytomegalovirus (HCMV) cause significant morbidity and mortality. These viruses replicate within and shed from mucosal organs such as the salivary glands. A significant aspect of our research to date has investigated the immune mechanisms that allow virus persistence within mucosal tissues and identify how they suppress antiviral immune responsiveness.
Using the murine cytomegalovirus (mCMV) model of infection, we discovered that production of the immune regulatory cytokine IL-10 by T cells is a hallmark of chronic viral infection (Humphreys et al, J Exp Med, 2007), and IL-10 suppresses antiviral immunity during mucosal viral persistence (Humphreys et al, J Exp Med, 2007) and viral latency (Jones et al, J Immunol, 2010). We have identified that virus-specific T cells in mucosal and non-mucosal tissues in mice and humans secrete IL-10, and identified that T cell production of IL-10, which is triggered by the cytokine IL-27, promotes virus persistence and shedding from the mucosa through suppression of antiviral T cell accumulation (Clement et al, PLoS Pathogens, 2016).
We also discovered that ineffectual antiviral immunity within the mucosa was due, in part, to suboptimal proliferation of mucosal myeloid cells and observed that the inhibitory CD200 receptor (CD200R), expressed by myeloid cells residing within the salivary glands, restricted myeloid cell proliferation triggered by mCMV, and subsequently suppressed anti-viral T cell immunity. This finding suggested that herpesviruses that encode functional homologues of the CD200R ligand might do so to exploit this immune regulatory process. This study also suggested that enhancing myeloid cell proliferation within mucosal tissues improves the induction of mucosal anti-viral T cell responses (Stack et al, PLoS Pathogens, 2015).
Early cytokine-mediated control of virus-induced immune responses:
Our research also studies how early cytokine responses influence antiviral immune responses. We discovered that, despite its suppressive activities, IL-10 promotes NK cell immunity via restriction of activation-induced cell death (Stacey et al, J Immunol, 2011). Further, we identified that the IL-10-related cytokine IL-22 exerts tissue-specific control of mCMV replication. We found that neutrophils induced by IL-22 act as efficient antiviral effector cells that restrict mCMV replication during acute infections in certain tissues (lung and liver).
We are also interested in how early immune signals could be harnessed to improve virus-induced immune responses. We have discovered that the alarmin IL-33 acts early to improve virus-induced T cell responses, demonstrating the possible utility of cytokines as adjuvants in vaccine strategies using viral vectors (Mclaren et al, J Immunol, 2019 - Top 10 most-read papers 2019).
Regulation of Viral Pathogenesis:
Our laboratory also aims to identify what mechanisms regulate cytokine-driven viral pathogenesis. In studies facilitated by an extensive and on-going collaboration with the Wellcome Trust Sanger Institute, we discovered that an intrinsic immune protein, interferon-induced transmembrane protein 3 (Ifitm3), restricts cytokine-mediated viral pathogenesis independently of direct antiviral control that is typically considered the primary function of intrinsic immune proteins (Stacey et al, J Clin Invest, 2017). IL-6, a cytokine that we helped identify as a central inflammatory mediator of fibrosis (Fielding et al, Immunity, 2014), exacerbated mCMV-induced inflammation despite also being required for the generation of cellular antiviral immune responses. These data highlighted that early control of pro-inflammatory cytokines is crucial for balancing antiviral immunity and viral-induced immune pathogenesis. A minor allele of Ifitm3, which is implicated in reduced Ifitm3 function, is a risk factor for viral pathogenesis in humans. Thus, this finding highlights the potential importance of anti-inflammatory therapies in personalized treatment of viral pathogenesis in genetically susceptible individuals. We have developed human myeloid cell models using stem cell technology that enable genetic studies of the cellular factors that influence virus-induced inflammatory responses (Forbester et al, J Vir, 2020).
COVID-19
I am Cardiff Lead in the UK-COVID19 Immunology Consoortium (UK-CIC), studying the role of the immune response in SARS-CoV-2 infection, with specific projects in this area including identification of markers predictive of COVID-19 outcome.
Teaching
ME3030 Microbial pathogenesis
ME3045 Advanced Immunology
Virology Tutor, C21
SSC Year 1 Tutor – Literature Projects
SSC Year 2 – Laboratory Placement Supervisor
Small Group (PCS) Tutor
Academic Mentoring
Biography
Education and Qualifications:
- 2004: PhD in Biochemistry, Centre of Molecular Microbiology and Infection, Imperial College London
- 2000: BSc in Biological Sciences with Virology, University of Warwick
Career Overview:
Cardiff University, UK (2007-Present):
- 2021-Present: Director, Systems Immunity University Research Institute
- 2018-Present: Professor of Viral Pathogenesis
- 2012-Present: Wellcome Trust Senior Research Fellow
- 2007-2012: Wellcome Trust Research Career Development Fellow
La Jolla Institute for Allergy and Immunology, San Diego USA:
- 2000-2004: Postdoctoral Researcher
Imperial College London, UK:
- 2004: Postdoctoral Researcher
- 2000-2004: PhD Student
Honours and awards
Major Honours and Distinctions:
- 2017: Awarded a Renewal of a Wellcome Trust Senior Fellowship in Basic Biomedical Science
- 2016: Appointed Member of the British Society of Immunology Congress Committee
- 2014: Appointed Member of the Wellcome Trust Basic Science Interview Committee
- 2013: Appointed as Honorary Faculty at the Wellcome Trust Sanger Institute
- 2012: Wellcome Trust Senior Fellowship in Basic Biomedical Science
- 2007: Wellcome Trust Research Career Development Fellowship
Professional memberships
- British Society of Immunology (BSI)
- International Cytokine Society (ICS)
- Society of General Microbiology
Academic positions
La Jolla Institute for Allergy and Immunology, San Diego USA:
2004-2006: Postdoctoral Scientist working with Professors Carl Ware and Mick Croft investigating the role of TNF and TNF receptor family members in T cell responses to cytomegalovirus infection.
Imperial College London, UK:
2004: Postdoctoral scientist working with Professor Douglas Young studying the dissemination of mycobacteria in vivo.
Committees and reviewing
- 2020: Immune System in Health and Disease Expert Review Group, Wellcome Trust
- 2016-2020: British Society for Immunology, Congress Committee
- 2014-2019: Wellcome Trust Basic Science Interview Committee
Engagement
I am a member of the Welsh Government International Intelligence group, providing insight into the COVID-19 pandemic. In response to the COVID-19 pandemic, I have been engaging with numerous companies regarding SARS-CoV-2 research projects.
I have 18 years' experience of undertaking public engagement. I run a series of activities in primary schools including microscopic analysis of immune cells, performing experiments and using Lego to teach people of all ages about complex immunological concepts in a simple manner. My laboratory also coordinates the immunology section of the highly successful Science in Health Live! event promoting biomedical research to A-Level students. Participating students experience the laboratory setting and learn about harnessing the immune system to treat diseases and the different cutting edge technologies utilised in the lab.
Contact Details
+44 29206 87076
Henry Wellcome Building for Biomedical Research, Room 3F08, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN