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

doi:10.4049/jimmunol.1600940

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Gut Microbial Membership Modulates CD4 T Cell Reconstitution and Function after Sepsis

Journal article

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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 and Thomas S Griffith

The Journal of immunology (1950), Vol.197(5), pp.1692-1698

09/01/2016

DOI: 10.4049/jimmunol.1600940

PMCID: PMC4992581

PMID: 27448587

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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 SFB(-), 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.

Sepsis - immunology

Mice, Inbred C57BL

Antigens, Bacterial - immunology

Lymphopenia - complications

CD4-Positive T-Lymphocytes - immunology

Listeria - immunology

Animals

Flow Cytometry

Intestines - microbiology

Cecum - surgery

Mice

Gastrointestinal Microbiome - immunology

Listeria - chemistry

Listeria - pathogenicity

Sepsis - microbiology

Details

Title: Subtitle: Gut Microbial Membership Modulates CD4 T Cell Reconstitution and Function after Sepsis
Creators: Javier Cabrera-Perez - Microbiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota, Minneapolis, MN 55455; Medical Scientist Training Program, University of Minnesota, Minneapolis, MN 55455
Jeffrey C Babcock - Medical Student Summer Research Program in Infection and Immunity, University of Minnesota, Minneapolis, MN 55455
Thamotharampillai Dileepan - Center for Immunology, University of Minnesota, Minneapolis, MN 55455
Katherine A Murphy - Department of Urology, University of Minnesota, Minneapolis, MN 55455
Tamara A Kucaba - Department of Urology, University of Minnesota, Minneapolis, MN 55455
Vladimir P Badovinac - Department of Pathology, University of Iowa, Iowa City, IA 52242; Interdisciplinary Program in Immunology, University of Iowa, Iowa City, IA 52242
Thomas S Griffith - Microbiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota, Minneapolis, MN 55455; Center for Immunology, University of Minnesota, Minneapolis, MN 55455; Department of Urology, University of Minnesota, Minneapolis, MN 55455; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455; and Minneapolis VA Health Care System, Minneapolis, MN 55417 tgriffit@umn.edu
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.197(5), pp.1692-1698
DOI: 10.4049/jimmunol.1600940
PMID: 27448587
PMCID: PMC4992581
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: I01 BX001324 / BLRD VA R01 AI114543 / NIAID NIH HHS R21 AI119160 / NIAID NIH HHS R01 GM113961 / NIGMS NIH HHS P30 CA077598 / NCI NIH HHS T35 AI118620 / NIAID NIH HHS P30 CA086862 / NCI NIH HHS R01 GM115462 / NIGMS NIH HHS T32 AI007313 / NIAID NIH HHS
Language: English
Date published: 09/01/2016
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984047784902771

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