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环磷酰胺治疗在免疫功能低下个体中模拟亚致死性感染。

Cyclophosphamide Treatment Mimics Sub-Lethal Infections With in Immunocompromised Individuals.

作者信息

de Moura Maria Lucia Costa, Alvares-Saraiva Anuska Marcelino, Pérez Elizabeth Cristina, Xavier José Guilherme, Spadacci-Morena Diva Denelle, Moysés Carla Renata Serantoni, Rocha Paulo Ricardo Dell'Armelina, Lallo Maria Anete

机构信息

Programa de Pós-Graduação em Patologia Ambiental e Experimental, Universidade Paulista (UNIP), São Paulo, Brazil.

Departamento de Fisiopatologia, Instituto Butantan, São Paulo, Brazil.

出版信息

Front Microbiol. 2019 Sep 25;10:2205. doi: 10.3389/fmicb.2019.02205. eCollection 2019.

Abstract

Microsporidia, including , are emerging pathogens which cause opportunistic infections in immunocompromised patients, such as those with AIDS, cancer, the elderly and people on immunosuppressive drugs. Intestinal mucosa (IM) is crucial for developing an efficient adaptive immune response against pathogenic micro-organisms, thereby preventing their colonization and subsequent infection. As immunosuppressive drugs affect the intestinal immune response is little known. In the present study, we investigated the immune response to infection in the IM and gut-associated lymphoid tissue (GALT) in cyclophosphamide (Cy) immunosuppressed mice, to mimic an immunocompromised condition. Histopathology revealed lymphoplasmacytic enteritis at 7 and 14 days-post-infection (dpi) in all infected groups, however, inflammation diminished at 21 and 28 dpi. Cy treatment also led to a higher number of spores and lesions, which reduced at 28 dpi. In addition, flow cytometry analysis demonstrated CD4 and CD8 T cells to be predominant immune cells, with up-regulation in both Th1 and Th2 cytokines at 7 and 14 dpi, as demonstrated by histopathology. In conclusion, Cy treatment reduced GALT (Peyer's plaques and mesenteric lymph nodes) and peritoneum populations but increased the T-cell population in the intestinal mucosa and the production of pro-and anti-inflammatory cytokines, which were able to eliminate this opportunistic fungus and reduced the infection.

摘要

微孢子虫,包括 ,是新兴的病原体,可在免疫功能低下的患者中引起机会性感染,如艾滋病患者、癌症患者、老年人以及服用免疫抑制药物的人。肠黏膜(IM)对于针对病原微生物产生有效的适应性免疫反应至关重要,从而防止它们定植并随后感染。免疫抑制药物如何影响肠道免疫反应尚不清楚。在本研究中,我们在环磷酰胺(Cy)免疫抑制的小鼠中研究了IM和肠道相关淋巴组织(GALT)对 感染的免疫反应,以模拟免疫功能低下的状况。组织病理学显示,所有感染组在感染后7天和14天(dpi)出现淋巴浆细胞性肠炎,然而,在21天和28天dpi时炎症减轻。Cy治疗还导致 孢子和病变数量增加,在28天dpi时减少。此外,流式细胞术分析表明CD4和CD8 T细胞是主要的免疫细胞,如组织病理学所示,在7天和14天dpi时Th1和Th2细胞因子均上调。总之,Cy治疗减少了GALT(派尔集合淋巴结和肠系膜淋巴结)和腹膜中的细胞数量,但增加了肠黏膜中的T细胞数量以及促炎和抗炎细胞因子的产生,这些能够消除这种机会性真菌并减少 感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3727/6773878/8b624b7a8592/fmicb-10-02205-g001.jpg

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