Frontiers in Immunology (Oct 2018)

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,
  • Derek B. Danahy,
  • Tamara A. Kucaba,
  • Lorraine T. Tygrett,
  • Katherine A. Murphy,
  • Javier Cabrera-Perez,
  • Javier Cabrera-Perez,
  • Thomas J. Waldschmidt,
  • Vladimir P. Badovinac,
  • Vladimir P. Badovinac,
  • Vladimir P. Badovinac,
  • Thomas S. Griffith,
  • Thomas S. Griffith,
  • Thomas S. Griffith,
  • Thomas S. Griffith,
  • Thomas S. Griffith

DOI
https://doi.org/10.3389/fimmu.2018.02532
Journal volume & issue
Vol. 9

Abstract

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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 2W1S56−68 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.

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