Systemic Inflammation Suppresses Lymphoid Tissue Remodeling and B Cell Immunity during Concomitant Local Infection

Cell Rep. 2020 Dec 29;33(13):108567. doi: 10.1016/j.celrep.2020.108567.

Abstract

Concurrent infection with multiple pathogens occurs frequently in individuals and can result in exacerbated infections and altered immunity. However, the impact of such coinfections on immune responses remains poorly understood. Here, we reveal that systemic infection results in an inflammation-induced suppression of local immunity. During localized infection or vaccination in barrier tissues including the skin or respiratory tract, concurrent systemic infection induces a type I interferon-dependent lymphopenia that impairs lymphocyte recruitment to the draining lymph node (dLN) and induces sequestration of lymphocytes in non-draining LN. This contributes to suppressed fibroblastic reticular cell and endothelial cell expansion and dLN remodeling and impairs induction of B cell responses and antibody production. Our data suggest that contemporaneous systemic inflammation constrains the induction of regional immunity.

Keywords: B cells; fibroblastic reticular cells; immune response; inflammation; lymph node; lymphoid stromal cells; lymphopenia; pathogen coinfection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation
  • Coinfection / immunology*
  • Fibroblasts / immunology
  • Herpes Simplex / immunology*
  • Herpes Simplex / virology
  • Inflammation / immunology*
  • Interferon Type I / metabolism
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Lymphocytic Choriomeningitis / immunology*
  • Lymphocytic Choriomeningitis / virology
  • Lymphocytic choriomeningitis virus / immunology*
  • Lymphoid Tissue / immunology*
  • Lymphoid Tissue / metabolism
  • Lymphopenia / immunology
  • Mice
  • Mice, Inbred C57BL
  • Simplexvirus / immunology*
  • Stromal Cells / immunology
  • Stromal Cells / metabolism

Substances

  • Interferon Type I