Polymicrobial Sepsis Chronic Immunoparalysis Is Defined by Diminished Ag-Specific T Cell-Dependent B Cell Responses

Frances V Sjaastad; Stephanie A Condotta; Jessica A Kotov; Kathryn A Pape; Cody Dail; Derek B Danahy; Tamara A Kucaba; Lorraine T Tygrett; Katherine A Murphy; Javier Cabrera-Perez; Thomas J Waldschmidt; Vladimir P Badovinac; Thomas S Griffith

doi:10.3389/fimmu.2018.02532

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Polymicrobial Sepsis Chronic Immunoparalysis Is Defined by Diminished Ag-Specific T Cell-Dependent B Cell Responses

Journal article

Open access

Peer reviewed

Polymicrobial Sepsis Chronic Immunoparalysis Is Defined by Diminished Ag-Specific T Cell-Dependent B Cell Responses

Frances V Sjaastad, Stephanie A Condotta, Jessica A Kotov, Kathryn A Pape, Cody Dail, Derek B Danahy, Tamara A Kucaba, Lorraine T Tygrett, Katherine A Murphy, Javier Cabrera-Perez, …

Frontiers in immunology, Vol.9, pp.2532-2532

2018

DOI: 10.3389/fimmu.2018.02532

PMCID: PMC6220049

PMID: 30429857

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Abstract

Immunosuppression is one hallmark of sepsis, decreasing the host response to the primary septic pathogens and/or secondary nosocomial infections. CD4 T cells and B cells are among the array of immune cells that experience reductions in number and function during sepsis. "Help" from follicular helper (Tfh) CD4 T cells to B cells is needed for productive and protective humoral immunity, but there is a paucity of data defining the effect of sepsis on a primary CD4 T cell-dependent B cell response. Using the cecal ligation and puncture (CLP) mouse model of sepsis induction, we observed reduced antibody production in mice challenged with influenza A virus or TNP-KLH in alum early (2 days) and late (30 days) after CLP surgery compared to mice subjected to sham surgery. To better understand how these CD4 T cell-dependent B cell responses were altered by a septic event, we immunized mice with a Complete Freund's Adjuvant emulsion containing the MHC II-restricted peptide 2W1S coupled to the fluorochrome phycoerythrin (PE). Immunization with 2W1S-PE/CFA results in T cell-dependent B cell activation, giving us the ability to track defined populations of antigen-specific CD4 T cells and B cells responding to the same immunogen in the same mouse. Compared to sham mice, differentiation and class switching in PE-specific B cells were blunted in mice subjected to CLP surgery. Similarly, mice subjected to CLP had reduced expansion of 2W1S-specific T cells and Tfh differentiation after immunization. Our data suggest CLP-induced sepsis impacts humoral immunity by affecting the number and function of both antigen-specific B cells and CD4 Tfh cells, further defining the period of chronic immunoparalysis after sepsis induction.

Influenza A virus - physiology

Sepsis - immunology

Antibodies - metabolism

Cytokines - metabolism

Lymphocyte Activation

Coinfection - immunology

Mice, Inbred C57BL

Antigens, Bacterial - immunology

Cells, Cultured

Immune Tolerance

Animals

B-Lymphocytes - immunology

Cecum - surgery

T-Lymphocytes, Helper-Inducer - immunology

Female

Cell Differentiation

Mice

Chronic Disease

Orthomyxoviridae Infections - immunology

Disease Models, Animal

Details

Title: Subtitle: Polymicrobial Sepsis Chronic Immunoparalysis Is Defined by Diminished Ag-Specific T Cell-Dependent B Cell Responses
Creators: Frances V Sjaastad - Microbiology, Immunology, and Cancer Biology Ph.D. Program, University of Minnesota, Minneapolis, MN, United States
Stephanie A Condotta - Department of Pathology, University of Iowa, Iowa City, IA, United States
Jessica A Kotov - Microbiology, Immunology, and Cancer Biology Ph.D. Program, University of Minnesota, Minneapolis, MN, United States
Kathryn A Pape - Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, United States
Cody Dail - Medical Student Summer Research Program in Infection and Immunity, University of Minnesota, Minneapolis, MN, United States
Derek B Danahy - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA, United States
Tamara A Kucaba - Department of Urology, University of Minnesota, Minneapolis, MN, United States
Lorraine T Tygrett - Department of Pathology, University of Iowa, Iowa City, IA, United States
Katherine A Murphy - Department of Urology, University of Minnesota, Minneapolis, MN, United States
Javier Cabrera-Perez - Medical Scientist Training Program, University of Minnesota, Minneapolis, MN, United States
Thomas J Waldschmidt - Department of Pathology, University of Iowa, Iowa City, IA, United States
Vladimir P Badovinac - Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, United States
Thomas S Griffith - Minneapolis VA Health Care System, Minneapolis, MN, United States
Resource Type: Journal article
Publication Details: Frontiers in immunology, Vol.9, pp.2532-2532
DOI: 10.3389/fimmu.2018.02532
PMID: 30429857
PMCID: PMC6220049
NLM abbreviation: Front Immunol
ISSN: 1664-3224
eISSN: 1664-3224
Publisher: Switzerland
Grant note: T35 AI118620 / NIAID NIH HHS T32 CA009138 / NCI NIH HHS T32 AI007485 / NIAID NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 2018
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984046801702771

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