Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland.
J Infect Dis. 2024 Oct 16;230(4):1033-1041. doi: 10.1093/infdis/jiae133.
CD40-CD40 ligand interactions are critical for controlling Pneumocystis infection. However, which CD40-expressing cell populations are important for this interaction have not been well defined. We used a cohousing mouse model of Pneumocystis infection, combined with flow cytometry and quantitative polymerase chain reaction, to examine the ability of different populations of cells from C57BL/6 mice to reconstitute immunity in CD40 knockout mice. Unfractionated splenocytes, as well as purified B cells, were able to control Pneumocystis infection, while B cell-depleted splenocytes and unstimulated bone marrow-derived dendritic cells were unable to control infection in CD40 knockout mice. Pneumocystis antigen-pulsed bone marrow-derived dendritic cells showed early but limited control of infection. Additional findings were consistent with recent studies that suggested a role for antigen presentation by B cells; specifically, by using cells from immunized animals, B cells were able to present Pneumocystis antigens to induce proliferation of T cells. Thus, CD40 expression by B cells appears necessary for robust immunity to Pneumocystis.
CD40-CD40 配体相互作用对于控制肺孢子菌感染至关重要。然而，哪种表达 CD40 的细胞群体对于这种相互作用很重要，尚未得到很好的定义。我们使用肺孢子菌感染的共笼小鼠模型，结合流式细胞术和定量聚合酶链反应，研究来自 C57BL/6 小鼠的不同细胞群体在 CD40 敲除小鼠中重建免疫的能力。未分馏的脾细胞以及纯化的 B 细胞能够控制肺孢子菌感染，而 B 细胞耗尽的脾细胞和未刺激的骨髓来源的树突状细胞无法控制 CD40 敲除小鼠的感染。肺孢子菌抗原脉冲骨髓来源的树突状细胞显示出早期但有限的感染控制。其他发现与最近的研究一致，表明 B 细胞具有抗原呈递作用；具体而言，使用免疫动物的细胞，B 细胞能够呈递肺孢子菌抗原以诱导 T 细胞增殖。因此，B 细胞表达 CD40 似乎是对肺孢子菌产生强大免疫所必需的。
