IL-10-producing B cells regulate Th1/Th17-cell immune responses in Pneumocystis pneumonia
IL-10-producing B cells regulate Th1/Th17-cell immune responses in Pneumocystis pneumonia
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产生 IL-10 的 B 细胞调节肺孢子虫肺炎中 Th1/Th17 细胞的免疫反应
DOI：
10.1152/ajplung.00210.2018
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发表时间：
2019-01-01
影响因子：
4.9
通讯作者：
Tong, Zhao-Hui
中科院分区：
文献类型：
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作者：
Rong, Heng-Mo;Li, Ting;Tong, Zhao-Hui
肺孢子虫肺炎(PCP)是一种常见的机会性传染病，在免疫抑制的宿主中流行。越来越多的证据表明，B细胞在传染病中发挥着重要作用。本研究评价了成熟B细胞在宿主防御肺孢子虫中的免疫调节作用。肺孢子虫感染导致患者和小鼠的B细胞减少，B细胞缺陷小鼠的肺孢子虫负担也从感染后1周到7周逐渐增加。B细胞活化因子受体(BAFF-R)缺陷小鼠(BAFF-R-/-小鼠)的B细胞和肺孢子虫特异性的Ig G和Ig M抗体较少，与野生型(WT)小鼠相比，BAFF-R-/-小鼠对肺孢子虫的清除延迟。BAFF-R-/-小鼠较WT小鼠有较少的效应CD4(+)T细胞和较高比例的辅助性T细胞(Th)1/Th17。过继转移幼稚B细胞、mRNA测序和IL-1β中和实验表明，IL-1β可能是产生IL-10的B细胞介导的抑制BAFF-R-/-PCP小鼠Th1/Th17细胞免疫应答的决定因素。我们的数据表明，B细胞在调节Th细胞对肺孢子虫感染的反应中起着至关重要的作用。
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-1 beta neutralization experiments indicated that IL-1 beta 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.