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

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.