Leishmania braziliensis exosomes activate human macrophages to produce proinflammatory mediators.
Leishmania braziliensis exosomes activate human macrophages to produce proinflammatory mediators.
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DOI：
10.3389/fimmu.2023.1256425
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发表时间：
2023
影响因子：
7.3
通讯作者：
Carvalho, Lucas P.
中科院分区：
文献类型：
--
作者：
Peixoto, Fabio C.;Zanette, Dalila L.;Cardoso, Thiago M.;Nascimento, Mauricio T.;Sanches, Rodrigo C. O.;Aoki, Mateus;Scott, Phillip;Oliveira, Sergio C.;Carvalho, Edgar M.;Carvalho, Lucas P.
外泌体是一种直径为30- 200 nm的细胞器，由多种细胞分泌。利什曼原虫外泌体由许多蛋白质组成，包括热休克蛋白、膜联蛋白、糖蛋白63、发挥信号传导活性的蛋白质以及含有mRNA和miRNA的蛋白质。研究表明，杜氏利什曼原虫外泌体下调IFN-γ并抑制杀微生物分子如TNF和一氧化氮的表达，从而创造有利于寄生虫增殖的微环境。尽管缺乏免疫记忆，但文献中的数据表明，在初始刺激后，单核吞噬细胞可能会变得“训练有素”，以更有效地响应随后的刺激。在这里，我们使用L.在被相同病原体感染之前，巴西人的外泌体。用L. braziliensis外泌体，然后感染L.巴西。与未刺激的感染细胞相比，在感染前致敏的培养物中检测到更高水平的IL-1β和IL-6。此外，L.巴西外泌体诱导巨噬细胞产生IL-1β、IL-6、IL-10和TNF。外泌体分泌的抑制作用。在巨噬细胞感染之前，巴西红细胞减少了细胞因子的产生，并且产生了比未处理的感染细胞更低的感染率。外泌体刺激还诱导巨噬细胞中NLRP 3炎性体组分的消耗/调节，而NLRP 3的阻断导致较低水平的IL-6和IL-1β。我们的结果表明L.巴西外泌体刺激巨噬细胞，导致可能是NLRP 3依赖性的加重的炎症状态。
Exosomes, organelles measuring 30-200nm, are secreted by various cell types. Leishmania exosomes consist of many proteins, including heat shock proteins, annexins, Glycoprotein 63, proteins exerting signaling activity and those containing mRNA and miRNA. Studies have demonstrated that Leishmania donovani exosomes downregulate IFN-γ and inhibit the expression of microbicidal molecules, such as TNF and nitric oxide, thus creating a microenvironment favoring parasite proliferation. Despite lacking immunological memory, data in the literature suggest that, following initial stimulation, mononuclear phagocytes may become “trained” to respond more effectively to subsequent stimuli. Here we characterized the effects of macrophage sensitization using L. braziliensis exosomes prior to infection by the same pathogen. Human macrophages were stimulated with L. braziliensis exosomes and then infected with L. braziliensis. Higher levels of IL-1β and IL-6 were detected in cultures sensitized prior to infection compared to unstimulated infected cells. Moreover, stimulation with L. braziliensis exosomes induced macrophage production of IL-1β, IL-6, IL-10 and TNF. Inhibition of exosome secretion by L. braziliensis prior to macrophage infection reduced cytokine production and produced lower infection rates than untreated infected cells. Exosome stimulation also induced the consumption/regulation of NLRP3 inflammasome components in macrophages, while the blockade of NLRP3 resulted in lower levels of IL-6 and IL-1β. Our results suggest that L. braziliensis exosomes stimulate macrophages, leading to an exacerbated inflammatory state that may be NLRP3-dependent.
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DOI：
10.4049/jimmunol.181.9.6473
发表时间：
2008-11-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Carvalho LP;Pearce EJ;Scott P
通讯作者：
Scott P
DOI：
10.1016/j.meegid.2017.01.018
发表时间：
2017-04
期刊：
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases
影响因子：
--
作者：
Almeida L;Silva JA;Andrade VM;Machado P;Jamieson SE;Carvalho EM;Blackwell JM;Castellucci LC
通讯作者：
Castellucci LC
影响因子：
6.4
作者：
Campos, Tais M.;Novais, Fernanda O.;Carvalho, Lucas P.
通讯作者：
Carvalho, Lucas P.
影响因子：
12.4
作者：
Gupta, Purnima;Srivastav, Supriya;Ukil, Anindita
通讯作者：
Ukil, Anindita
影响因子：
7.3
作者：
Carvalho LP;Passos S;Schriefer A;Carvalho EM
通讯作者：
Carvalho EM