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寄生虫抗原暴露增强了单核细胞和巨噬细胞中结核分枝杆菌的早期免疫控制。

Helminth Antigen Exposure Enhances Early Immune Control of Mycobacterium tuberculosis in Monocytes and Macrophages.

机构信息

Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.

Department of Infectious Diseases and Clinical Microbiology, Kalmar County Hospital, Kalmar, Sweden.

出版信息

J Innate Immun. 2021;13(3):148-163. doi: 10.1159/000512279. Epub 2020 Dec 17.

Abstract

Helminth and Mycobacterium tuberculosis (Mtb) coinfection is common and suggested to influence the risk of developing active tuberculosis (TB). It is known that helminths in contrast to TB induce a strong Th2 response in the host. However, the direct impact of helminth antigen exposure on host immunity against TB is largely unknown. Our aim was to explore the effects of helminth antigen exposure on the early immune control of Mtb in monocytes and macrophages. Ascaris lumbricoides (ASC) and Schistosoma mansoni (SM) protein antigens were used to study the immediate effect of helminth antigen exposure in monocytes, on monocyte-to-macrophage differentiation, or mature macrophages, in the control of virulent Mtb H37Rv. Pre-exposure of peripheral blood mononuclear cells reduced Mtb growth in monocytes, especially with SM, but no Th1/Th2 cytokines or activation markers indicated involvement of T cells. Monocytes exposed before maturing into macrophages reduced Mtb growth in macrophages (ASC), and pre-exposure of mature macrophages reduced (ASC) or kept Mtb growth at control levels (SM). This in vitro model shows how helminth infection directly affects the monocyte-macrophage axis at an early stage before cell-mediated immunity develops. During acute helminth coinfection or when helminth antigen concentration is elevated at the site of Mtb infection, these helminths provide an enhanced control and killing of Mtb owing to the direct stimulatory effect of helminth antigens on phagocytic cells.

摘要

寄生虫和结核分枝杆菌(Mtb)的合并感染很常见,并被认为会影响发生活动性肺结核(TB)的风险。众所周知,与 TB 不同,寄生虫会在宿主中诱导强烈的 Th2 反应。然而,寄生虫抗原暴露对宿主针对 TB 的免疫的直接影响在很大程度上尚不清楚。我们的目的是探讨寄生虫抗原暴露对单核细胞和巨噬细胞中 Mtb 早期免疫控制的影响。使用蛔虫(ASC)和曼氏血吸虫(SM)蛋白抗原来研究寄生虫抗原暴露对单核细胞中单核细胞向巨噬细胞分化或成熟巨噬细胞控制毒力 Mtb H37Rv 的即时影响。外周血单核细胞的预暴露减少了单核细胞中的 Mtb 生长,尤其是用 SM 时,但没有 Th1/Th2 细胞因子或激活标志物表明 T 细胞的参与。在成熟为巨噬细胞之前暴露于 ASC 的单核细胞可减少巨噬细胞中的 Mtb 生长,而预暴露成熟的巨噬细胞可减少(ASC)或使 Mtb 生长保持在对照水平(SM)。该体外模型显示了寄生虫感染如何在细胞介导的免疫发展之前的早期阶段直接影响单核细胞-巨噬细胞轴。在急性寄生虫合并感染期间,或者当寄生虫抗原浓度在 Mtb 感染部位升高时,由于寄生虫抗原对吞噬细胞的直接刺激作用,这些寄生虫提供了对 Mtb 的增强控制和杀伤作用。

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