Gut microbial membership modulates CD4 T cell reconstitution and function after sepsis

Javier Cabrera-Perez, Jeffrey C. Babcock, Thamotharampillai Dileepan, Katherine A. Murphy, Tamara A. Kucaba, Vladimir P. Badovinac, Thomas S. Griffith

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Transient lymphopenia is one hallmark of sepsis, and emergent data indicate the CD4 T cell compartment in sepsis survivors is numerically and functionally altered (when examined at the Ag-specific level) compared with nonseptic control subjects. Previous data from our laboratory demonstrated Ag-independent, lymphopenia-induced homeostatic proliferation to be a contributing mechanism by which CD4 T cells numerically recover in sepsis survivors. However, we reasoned it is also formally possible that some CD4 T cells respond directly to Ag expressed by gut-resident microbes released during polymicrobial sepsis. The effect of gut microbiome leakage on CD4 T cells is currently unknown. In this study, we explored the number and function of endogenous CD4 T cells specific for segmented filamentous bacterium (SFB) after cecal ligation and puncture (CLP)-induced sepsis using mice that either contained or lacked SFB as a normal gut-resident microbe. Interestingly, SFB-specific CD4 T cells underwent Ag-driven proliferation in CLP-treated SFB+, but not in SFB2, mice. Moreover, CLP-treated SFB+ mice showed resistance to secondary lethal infection with recombinant SFB Ag-expressing virulent Listeria (but not wild-type virulent Listeria), suggesting the CLP-induced polymicrobial sepsis primed for a protective response by the SFB-specific CD4 T cells. Thus, our data demonstrate that the numerical recovery and functional responsiveness of Ag-specific CD4 T cells in sepsis survivors is, in part, modulated by the intestinal barrier's health discreetly defined by individual bacterial populations of the host's microbiome.

Original languageEnglish (US)
Pages (from-to)1692-1698
Number of pages7
JournalJournal of Immunology
Volume197
Issue number5
DOIs
StatePublished - Sep 1 2016

Bibliographical note

Funding Information:
This work was supported by a U.S. Department of Veterans Affairs Merit Review Award (to T.S.G.) and National Institutes of Health Grants T32AI007313 (to J.C.-P.), T35AI118620 (to J.C.B.), GM113961, AI119160, and AI114543 (to V.P.B.).

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