IL-10-producing B cells regulate Th1/Th17-cell immune responses in Pneumocystis pneumonia

Am J Physiol Lung Cell Mol Physiol. 2019 Jan 1;316(1):L291-L301. doi: 10.1152/ajplung.00210.2018. Epub 2018 Oct 4.

Abstract

Pneumocystis pneumonia (PCP) is a common opportunistic infectious disease that is prevalent in immunosuppressed hosts. Accumulating evidence shows that B cells play an important role in infectious diseases. In the present study, the immune regulatory role of mature B cells in host defense to Pneumocystis was evaluated. Pneumocystis infection resulted in a decrease in B cells in patients and mice, and the Pneumocystis burden in B cell-deficient mice also progressively increased from weeks 1 to 7 after infection. The clearance of Pneumocystis was delayed in B cell-activating factor receptor (BAFF-R)-deficient mice (BAFF-R-/- mice), which had few B cells and Pneumocystis-specific IgG and IgM antibodies, compared with clearance in wild-type (WT) mice. There were fewer effector CD4+ T cells and higher percentages of T helper (Th)1/Th17 cells in BAFF-R-/- mice than in WT mice. Adoptive transfer of naive B cells, mRNA sequencing, and IL-1β neutralization experiments indicated that IL-1β is a likely determinant of the IL-10-producing B cell-mediated suppression of Th1/Th17-cell immune responses in BAFF-R-/- PCP mice. Our data indicated that B cells play a vital role in the regulation of Th cells in response to Pneumocystis infection.

Keywords: pneumonia; B lymphocytes; IL-10; Th1 cells; Th17 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antibodies, Fungal / immunology
  • B-Cell Activation Factor Receptor / genetics
  • B-Cell Activation Factor Receptor / immunology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology
  • Female
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin M / immunology
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / immunology
  • Male
  • Mice
  • Mice, Knockout
  • Pneumocystis / immunology*
  • Pneumonia, Pneumocystis / genetics
  • Pneumonia, Pneumocystis / immunology*
  • Pneumonia, Pneumocystis / pathology
  • Th1 Cells / immunology*
  • Th1 Cells / pathology
  • Th2 Cells / immunology*
  • Th2 Cells / pathology

Substances

  • Antibodies, Fungal
  • B-Cell Activation Factor Receptor
  • IL10 protein, human
  • IL10 protein, mouse
  • IL1B protein, human
  • IL1B protein, mouse
  • Immunoglobulin G
  • Immunoglobulin M
  • Interleukin-1beta
  • TNFRSF13C protein, human
  • Tnfrsf13c protein, mouse
  • Interleukin-10