IL-10-producing B cells regulate Th1/Th17-cell immune responses inPneumocystispneumonia

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.

Regulatory cytokine function in the respiratory tract

“…B cells are less well characterized than T cells as an IL-10 source during respiratory infection, but IL-10 + Bregs have been shown to limit pathogenic pulmonary Th1 and Th17 responses in a murine model of Pneumocystis infection. 104…”

Niflumic Acid Reverses Airway Mucus Excess and Improves Survival in the Rat Model of Steroid-Induced Pneumocystis Pneumonia

“…The more accepted explanation for this effect is that systemic use of corticosteroids leads to profound cell-mediated immunosuppression encompassing apoptosis of immune cells including CD4+, CD8+, and other T cell lymphocyte subsets (Walzer et al, 1984; Barnes, 2016). This blunting of the adaptive immune responses halts the clearance of the infection (Iwasaki and Medzhitov, 2015) and therefore, allows a growing fungal burden of Pneumocystis in the lungs (Screpanti et al, 1989; Adcock and Mumby, 2017; Hu et al, 2017; Rong et al, 2018) that keeps stimulating the airway epithelium (Screpanti et al, 1989; Swain et al, 2012; Eddens et al, 2016; Adcock and Mumby, 2017; Iturra et al, 2018). Collectively, available data suggest that Pneumocystis infection overcomes the anti-inflammatory effects of corticosteroids and induces a steroid-resistant mucus phenotype in this model.…”

IL-17 Inversely Correlated with IL-10 via the STAT3 Gene in Pneumocystis-Infected Mice

“…Pneumocystis murina was maintained in CB17 SCID mice, and lung homogenates were used to get Pneumocystis cysts as previously described [15, 26]. After the lung homogenates were stained using Diff-Quick (Baxter, McGaw Park, IL), the number of Pneumocystis cysts was determined microscopically.…”

“…Cells from tissue and blood were stained with innate cell-specific, B cell-specific, and T cell-specific panels, as described previously [15], and analyzed using FACSCanto II (BD Biosciences, San Jose, CA, USA). The antibody panel is described in the online supplement.…”

“…Nowadays, accumulating evidence indicates that B cells might play a vital role of promoting the proliferation and activation of CD4 + T cells during Pneumocystis infection [14]. Our previous study also demonstrated that B10 cells regulated the Th1/Th17 cell immune responses in the PCP model [15].…”