Polymicrobial Sepsis Impairs Antigen-Specific Memory CD4 T Cell-Mediated Immunity

Frances V Sjaastad; Tamara A Kucaba; Thamotharampillai Dileepan; Whitney Swanson; Cody Dail; Javier Cabrera-Perez; Katherine A Murphy; Vladimir P Badovinac; Thomas S Griffith

doi:10.3389/fimmu.2020.01786

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Polymicrobial Sepsis Impairs Antigen-Specific Memory CD4 T Cell-Mediated Immunity

Journal article

Open access

Peer reviewed

Polymicrobial Sepsis Impairs Antigen-Specific Memory CD4 T Cell-Mediated Immunity

Frances V Sjaastad, Tamara A Kucaba, Thamotharampillai Dileepan, Whitney Swanson, Cody Dail, Javier Cabrera-Perez, Katherine A Murphy, Vladimir P Badovinac and Thomas S Griffith

Frontiers in immunology, Vol.11, pp.1786-1786

2020

DOI: 10.3389/fimmu.2020.01786

PMCID: PMC7435018

PMID: 32903436

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Abstract

Patients who survive sepsis display prolonged immune dysfunction and heightened risk of secondary infection. CD4 T cells support a variety of cells required for protective immunity, and perturbations to the CD4 T cell compartment can decrease overall immune system fitness. Using the cecal ligation and puncture (CLP) mouse model of sepsis, we investigated the impact of sepsis on endogenous Ag-specific memory CD4 T cells generated in C57BL/6 (B6) mice infected with attenuated (Lm) expressing the I-A -restricted 2W1S epitope (Lm-2W). The number of 2W1S-specific memory CD4 T cells was significantly reduced on day 2 after sepsis induction, but recovered by day 14. In contrast to the transient numerical change, the 2W1S-specific memory CD4 T cells displayed prolonged functional impairment after sepsis, evidenced by a reduced recall response (proliferation and effector cytokine production) after restimulation with cognate Ag. To define the extent to which the observed functional impairments in the memory CD4 T cells impacts protection to secondary infection, B6 mice were infected with attenuated 2W ( -2W) 30 days before sham or CLP surgery, and then challenged with virulent 2W after surgery. Pathogen burden was significantly higher in the CLP-treated mice compared to shams. Similar reductions in functional capacity and protection were noted for the endogenous OVA -specific memory CD4 T cell population in sepsis survivors upon Lm-OVA challenge. Our data collectively show CLP-induced sepsis alters the number and function of Ag-specific memory CD4 T cells, which contributes (in part) to the characteristic long-lasting immunoparalysis seen after sepsis.

Animals

Antigens, Bacterial - immunology

CD4-Positive T-Lymphocytes - immunology

CD4-Positive T-Lymphocytes - metabolism

CD4-Positive T-Lymphocytes - microbiology

Cecum - microbiology

Cecum - surgery

Cell Proliferation

Coinfection - immunology

Coinfection - metabolism

Coinfection - microbiology

Cytokines - metabolism

Disease Models, Animal

Female

Host-Pathogen Interactions

Immunity, Cellular

Immunologic Memory

Ligation

Listeria monocytogenes - immunology

Listeria monocytogenes - pathogenicity

Listeriosis - immunology

Listeriosis - metabolism

Listeriosis - microbiology

Lymphocyte Activation

Mice, Inbred C57BL

Punctures

Salmonella enterica - immunology

Salmonella enterica - pathogenicity

Salmonella Infections - immunology

Salmonella Infections - metabolism

Salmonella Infections - microbiology

Sepsis - immunology

Sepsis - metabolism

Sepsis - microbiology

Details

Title: Subtitle: Polymicrobial Sepsis Impairs Antigen-Specific Memory CD4 T Cell-Mediated Immunity
Creators: Frances V Sjaastad - University of Minnesota
Tamara A Kucaba - University of Minnesota
Thamotharampillai Dileepan - University of Minnesota
Whitney Swanson - University of Minnesota
Cody Dail - University of Minnesota
Javier Cabrera-Perez - University of Minnesota
Katherine A Murphy - University of Minnesota
Vladimir P Badovinac - University of Iowa
Thomas S Griffith - University of Minnesota
Resource Type: Journal article
Publication Details: Frontiers in immunology, Vol.11, pp.1786-1786
DOI: 10.3389/fimmu.2020.01786
PMID: 32903436
PMCID: PMC7435018
NLM abbreviation: Front Immunol
ISSN: 1664-3224
eISSN: 1664-3224
Grant note: P30 CA077598 / NCI NIH HHS T35 AI118620 / NIAID NIH HHS R35 GM134880 / NIGMS NIH HHS T32 CA009138 / NCI NIH HHS R01 GM115462 / NIGMS NIH HHS T32 AI007313 / NIAID NIH HHS
Language: English
Date published: 2020
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984180924002771

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