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巴西副球孢子菌感染通过两种不同途径感染雌性 C57BL/6 小鼠会增加调节性 T 细胞计数。

Paracoccidioides brasiliensis infection increases regulatory T cell counts in female C57BL/6 mice infected via two distinct routes.

机构信息

Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil.

Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, SP, Brazil.

出版信息

Immunobiology. 2020 Jul;225(4):151963. doi: 10.1016/j.imbio.2020.151963. Epub 2020 May 31.

Abstract

Studies that show an overview of the peripheral immune response in a model of Paracoccidioides brasiliensis (Pb) infection in females are scarce in the literature. We sought to characterize the innate and adaptive immune responses in female C57BL/6 mice infected with Pb through two distinct routes of administration, intranasal and intravenous. In addition to the lung, P. brasiliensis yeast cells were observed in liver and brain tissues of females infected intravenously. To our knowledge, our study is the first to prove the presence of this pathogenic fungus in the cerebral cortex of female mice. During the initial stages of infection, augmented expression of both MHCII and CD86 was observed on the surface of CD11c pulmonary antigen-presenting cells (APCs) in intranasally and intravenously infected females. However, CD40 expression was downregulated in these cells. Concomitantly with increasing serum IL-10 levels, we noted that splenic dendritic cells (DCs) from both intravenously- and intranasally-infected female mice had acquired an immature phenotype. Further, increased T regulatory cell counts were observed in female mice infected via both routes, along with an increase in the infiltration of IL-10-producing CD8 T cells into the lungs. Moreover, we noted that P. brasiliensis infection resulted in enhanced IL-10 production - by CD11c APCs in the lung tissue - and induction of Th17 polarization. Taken together, our results suggest that P. brasiliensis could modulates the immune response in female mice by influencing the balance between regulatory T cells (Tregs) and Th17 polarization.

摘要

研究表明,在巴西副球孢子菌(Pb)感染模型中,女性外周免疫反应的概述在文献中较为匮乏。我们试图通过两种不同的给药途径(鼻内和静脉内)来描述感染 Pb 的雌性 C57BL/6 小鼠的固有和适应性免疫反应。除了肺部,还观察到静脉内感染的女性肝脏和脑组织中有巴西副球孢子菌酵母细胞。据我们所知,我们的研究首次证明了这种致病真菌存在于雌性小鼠的大脑皮层中。在感染的早期阶段,鼻内和静脉内感染的雌性小鼠肺组织中 CD11c 呈递细胞(APC)表面的 MHCII 和 CD86 表达增强。然而,这些细胞中的 CD40 表达下调。同时,血清 IL-10 水平升高,我们注意到来自静脉内和鼻内感染的雌性小鼠的脾树突状细胞(DC)获得了不成熟的表型。此外,两种感染途径的雌性小鼠中调节性 T 细胞(Treg)计数增加,并且 IL-10 产生的 CD8 T 细胞浸润到肺部。此外,我们注意到巴西副球孢子菌感染导致肺组织中 CD11c APC 产生的 IL-10 增加,并诱导 Th17 极化。综上所述,我们的结果表明,巴西副球孢子菌可能通过影响调节性 T 细胞(Treg)和 Th17 极化之间的平衡来调节雌性小鼠的免疫反应。

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