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Discordant rearrangement of primary and anamnestic CD8(+) T cell responses to influenza A viral epitopes upon exposure to bacterial superantigens: Implications for prophylactic vaccination, heterosubtypic immunity and superinfections

Infection with (SAg)-producing bacteria may precede or follow infection with or vaccination against influenza A viruses (IAVs). However, how SAgs alter the breadth of IAV-specific CD8(+) T cell (T(CD8)) responses is unknown. Moreover, whether recall responses mediating heterosubtypic immunity to IAV...

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Autores principales: Meilleur, Courtney E., Memarnejadian, Arash, Shivji, Adil N., Benoit, Jenna M., Tuffs, Stephen W., Mele, Tina S., Singh, Bhagirath, Dikeakos, Jimmy D., Topham, David J., Mu, Hong-Hua, Bennink, Jack R., McCormick, John K., Haeryfar, S. M. Mansour
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239382/
https://www.ncbi.nlm.nih.gov/pubmed/32433711
http://dx.doi.org/10.1371/journal.ppat.1008393
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author Meilleur, Courtney E.
Memarnejadian, Arash
Shivji, Adil N.
Benoit, Jenna M.
Tuffs, Stephen W.
Mele, Tina S.
Singh, Bhagirath
Dikeakos, Jimmy D.
Topham, David J.
Mu, Hong-Hua
Bennink, Jack R.
McCormick, John K.
Haeryfar, S. M. Mansour
author_facet Meilleur, Courtney E.
Memarnejadian, Arash
Shivji, Adil N.
Benoit, Jenna M.
Tuffs, Stephen W.
Mele, Tina S.
Singh, Bhagirath
Dikeakos, Jimmy D.
Topham, David J.
Mu, Hong-Hua
Bennink, Jack R.
McCormick, John K.
Haeryfar, S. M. Mansour
author_sort Meilleur, Courtney E.
collection PubMed
description Infection with (SAg)-producing bacteria may precede or follow infection with or vaccination against influenza A viruses (IAVs). However, how SAgs alter the breadth of IAV-specific CD8(+) T cell (T(CD8)) responses is unknown. Moreover, whether recall responses mediating heterosubtypic immunity to IAVs are manipulated by SAgs remains unexplored. We employed wild-type (WT) and mutant bacterial SAgs, SAg-sufficient/deficient Staphylococcus aureus strains, and WT, mouse-adapted and reassortant IAV strains in multiple in vivo settings to address the above questions. Contrary to the popular view that SAgs delete or anergize T cells, systemic administration of staphylococcal enterotoxin B (SEB) or Mycoplasma arthritidis mitogen before intraperitoneal IAV immunization enlarged the clonal size of ‘select’ IAV-specific T(CD8) and reshuffled the hierarchical pattern of primary T(CD8) responses. This was mechanistically linked to the TCR Vβ makeup of the impacted clones rather than their immunodominance status. Importantly, SAg-expanded T(CD8) retained their IFN-γ production and cognate cytolytic capacities. The enhancing effect of SEB on immunodominant T(CD8) was also evident in primary responses to vaccination with heat-inactivated and live attenuated IAV strains administered intramuscularly and intranasally, respectively. Interestingly, in prime-boost immunization settings, the outcome of SEB administration depended strictly upon the time point at which this SAg was introduced. Accordingly, SEB injection before priming raised CD127(high)KLRG1(low) memory precursor frequencies and augmented the anamnestic responses of SEB-binding T(CD8). By comparison, introducing SEB before boosting diminished recall responses to IAV-derived epitopes drastically and indiscriminately. This was accompanied by lower Ki67 and higher Fas, LAG-3 and PD-1 levels consistent with a pro-apoptotic and/or exhausted phenotype. Therefore, SAgs can have contrasting impacts on anti-IAV immunity depending on the naïve/memory status and the TCR composition of exposed T(CD8). Finally, local administration of SEB or infection with SEB-producing S. aureus enhanced pulmonary T(CD8) responses to IAV. Our findings have clear implications for superinfections and prophylactic vaccination.
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spelling pubmed-72393822020-06-03 Discordant rearrangement of primary and anamnestic CD8(+) T cell responses to influenza A viral epitopes upon exposure to bacterial superantigens: Implications for prophylactic vaccination, heterosubtypic immunity and superinfections Meilleur, Courtney E. Memarnejadian, Arash Shivji, Adil N. Benoit, Jenna M. Tuffs, Stephen W. Mele, Tina S. Singh, Bhagirath Dikeakos, Jimmy D. Topham, David J. Mu, Hong-Hua Bennink, Jack R. McCormick, John K. Haeryfar, S. M. Mansour PLoS Pathog Research Article Infection with (SAg)-producing bacteria may precede or follow infection with or vaccination against influenza A viruses (IAVs). However, how SAgs alter the breadth of IAV-specific CD8(+) T cell (T(CD8)) responses is unknown. Moreover, whether recall responses mediating heterosubtypic immunity to IAVs are manipulated by SAgs remains unexplored. We employed wild-type (WT) and mutant bacterial SAgs, SAg-sufficient/deficient Staphylococcus aureus strains, and WT, mouse-adapted and reassortant IAV strains in multiple in vivo settings to address the above questions. Contrary to the popular view that SAgs delete or anergize T cells, systemic administration of staphylococcal enterotoxin B (SEB) or Mycoplasma arthritidis mitogen before intraperitoneal IAV immunization enlarged the clonal size of ‘select’ IAV-specific T(CD8) and reshuffled the hierarchical pattern of primary T(CD8) responses. This was mechanistically linked to the TCR Vβ makeup of the impacted clones rather than their immunodominance status. Importantly, SAg-expanded T(CD8) retained their IFN-γ production and cognate cytolytic capacities. The enhancing effect of SEB on immunodominant T(CD8) was also evident in primary responses to vaccination with heat-inactivated and live attenuated IAV strains administered intramuscularly and intranasally, respectively. Interestingly, in prime-boost immunization settings, the outcome of SEB administration depended strictly upon the time point at which this SAg was introduced. Accordingly, SEB injection before priming raised CD127(high)KLRG1(low) memory precursor frequencies and augmented the anamnestic responses of SEB-binding T(CD8). By comparison, introducing SEB before boosting diminished recall responses to IAV-derived epitopes drastically and indiscriminately. This was accompanied by lower Ki67 and higher Fas, LAG-3 and PD-1 levels consistent with a pro-apoptotic and/or exhausted phenotype. Therefore, SAgs can have contrasting impacts on anti-IAV immunity depending on the naïve/memory status and the TCR composition of exposed T(CD8). Finally, local administration of SEB or infection with SEB-producing S. aureus enhanced pulmonary T(CD8) responses to IAV. Our findings have clear implications for superinfections and prophylactic vaccination. Public Library of Science 2020-05-20 /pmc/articles/PMC7239382/ /pubmed/32433711 http://dx.doi.org/10.1371/journal.ppat.1008393 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Meilleur, Courtney E.
Memarnejadian, Arash
Shivji, Adil N.
Benoit, Jenna M.
Tuffs, Stephen W.
Mele, Tina S.
Singh, Bhagirath
Dikeakos, Jimmy D.
Topham, David J.
Mu, Hong-Hua
Bennink, Jack R.
McCormick, John K.
Haeryfar, S. M. Mansour
Discordant rearrangement of primary and anamnestic CD8(+) T cell responses to influenza A viral epitopes upon exposure to bacterial superantigens: Implications for prophylactic vaccination, heterosubtypic immunity and superinfections
title Discordant rearrangement of primary and anamnestic CD8(+) T cell responses to influenza A viral epitopes upon exposure to bacterial superantigens: Implications for prophylactic vaccination, heterosubtypic immunity and superinfections
title_full Discordant rearrangement of primary and anamnestic CD8(+) T cell responses to influenza A viral epitopes upon exposure to bacterial superantigens: Implications for prophylactic vaccination, heterosubtypic immunity and superinfections
title_fullStr Discordant rearrangement of primary and anamnestic CD8(+) T cell responses to influenza A viral epitopes upon exposure to bacterial superantigens: Implications for prophylactic vaccination, heterosubtypic immunity and superinfections
title_full_unstemmed Discordant rearrangement of primary and anamnestic CD8(+) T cell responses to influenza A viral epitopes upon exposure to bacterial superantigens: Implications for prophylactic vaccination, heterosubtypic immunity and superinfections
title_short Discordant rearrangement of primary and anamnestic CD8(+) T cell responses to influenza A viral epitopes upon exposure to bacterial superantigens: Implications for prophylactic vaccination, heterosubtypic immunity and superinfections
title_sort discordant rearrangement of primary and anamnestic cd8(+) t cell responses to influenza a viral epitopes upon exposure to bacterial superantigens: implications for prophylactic vaccination, heterosubtypic immunity and superinfections
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239382/
https://www.ncbi.nlm.nih.gov/pubmed/32433711
http://dx.doi.org/10.1371/journal.ppat.1008393
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