Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection

Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior...

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Veröffentlicht in:PLoS pathogens 2015-11, Vol.11 (11), p.e1005226
Hauptverfasser: Brown, Aisling F, Murphy, Alison G, Lalor, Stephen J, Leech, John M, O'Keeffe, Kate M, Mac Aogáin, Micheál, O'Halloran, Dara P, Lacey, Keenan A, Tavakol, Mehri, Hearnden, Claire H, Fitzgerald-Hughes, Deirdre, Humphreys, Hilary, Fennell, Jérôme P, van Wamel, Willem J, Foster, Timothy J, Geoghegan, Joan A, Lavelle, Ed C, Rogers, Thomas R, McLoughlin, Rachel M
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container_issue 11
container_start_page e1005226
container_title PLoS pathogens
container_volume 11
creator Brown, Aisling F
Murphy, Alison G
Lalor, Stephen J
Leech, John M
O'Keeffe, Kate M
Mac Aogáin, Micheál
O'Halloran, Dara P
Lacey, Keenan A
Tavakol, Mehri
Hearnden, Claire H
Fitzgerald-Hughes, Deirdre
Humphreys, Hilary
Fennell, Jérôme P
van Wamel, Willem J
Foster, Timothy J
Geoghegan, Joan A
Lavelle, Ed C
Rogers, Thomas R
McLoughlin, Rachel M
description Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior exposure to S. aureus enhanced IFNγ responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naïve mice. Translating these findings, we found that S. aureus antigen-specific Th1 cells were also significantly expanded during human S. aureus bloodstream infection (BSI). These Th1 cells were CD45RO+, indicative of a memory phenotype. Thus, exposure to S. aureus induces memory Th1 cells in mice and humans, identifying Th1 cells as potential S. aureus vaccine targets. Consequently, we developed a model vaccine comprising staphylococcal clumping factor A, which we demonstrate to be an effective human T cell antigen, combined with the Th1-driving adjuvant CpG. This novel Th1-inducing vaccine conferred significant protection during S. aureus infection in mice. This study notably advances our understanding of S. aureus cellular immunity, and demonstrates for the first time that a correlate of S. aureus protective immunity identified in mice may be relevant in humans.
doi_str_mv 10.1371/journal.ppat.1005226
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While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S. aureus peritonitis, we demonstrated that prior exposure to S. aureus enhanced IFNγ responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naïve mice. Translating these findings, we found that S. aureus antigen-specific Th1 cells were also significantly expanded during human S. aureus bloodstream infection (BSI). These Th1 cells were CD45RO+, indicative of a memory phenotype. Thus, exposure to S. aureus induces memory Th1 cells in mice and humans, identifying Th1 cells as potential S. aureus vaccine targets. Consequently, we developed a model vaccine comprising staphylococcal clumping factor A, which we demonstrate to be an effective human T cell antigen, combined with the Th1-driving adjuvant CpG. 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This study notably advances our understanding of S. aureus cellular immunity, and demonstrates for the first time that a correlate of S. aureus protective immunity identified in mice may be relevant in humans.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1005226</identifier><identifier>PMID: 26539822</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adjuvants, Immunologic - pharmacology ; Adoptive Transfer ; Adult ; Aged ; Animals ; Antigens ; Antigens - immunology ; Bacterial infections ; Bacteriology ; Care and treatment ; Clinical trials ; Complications and side effects ; Experiments ; Female ; Genetic diversity ; Genomes ; Health aspects ; Humans ; Immune system ; Immunologic Memory ; Influence ; Interferon ; Interleukin-17 - metabolism ; Lymphocytes ; Male ; Medical research ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Mortality ; Pathogens ; Staphylococcal Infections - immunology ; Staphylococcal Skin Infections - immunology ; Staphylococcal Skin Infections - microbiology ; Staphylococcus aureus - immunology ; Staphylococcus aureus infections ; Staphylococcus infections ; Th1 Cells - drug effects ; Th1 Cells - immunology ; Vaccines</subject><ispartof>PLoS pathogens, 2015-11, Vol.11 (11), p.e1005226</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Brown et al 2015 Brown et al</rights><rights>2015 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Infection. 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subjects Adjuvants, Immunologic - pharmacology
Adoptive Transfer
Adult
Aged
Animals
Antigens
Antigens - immunology
Bacterial infections
Bacteriology
Care and treatment
Clinical trials
Complications and side effects
Experiments
Female
Genetic diversity
Genomes
Health aspects
Humans
Immune system
Immunologic Memory
Influence
Interferon
Interleukin-17 - metabolism
Lymphocytes
Male
Medical research
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
Mortality
Pathogens
Staphylococcal Infections - immunology
Staphylococcal Skin Infections - immunology
Staphylococcal Skin Infections - microbiology
Staphylococcus aureus - immunology
Staphylococcus aureus infections
Staphylococcus infections
Th1 Cells - drug effects
Th1 Cells - immunology
Vaccines
title Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection
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