Capsular specific IgM enhances complement-mediated phagocytosis and killing of Cryptococcus neoformans by methamphetamine-treated J774.16 macrophage-like cells.
Capsular specific IgM enhances complement-mediated phagocytosis and killing of Cryptococcus neoformans by methamphetamine-treated J774.16 macrophage-like cells.
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DOI：
10.1016/j.intimp.2017.05.024
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发表时间：
2017-08
影响因子：
5.6
通讯作者：
Martinez LR
中科院分区：
文献类型：
--
作者：
Aslanyan L;Ekhar VV;DeLeon-Rodriguez CM;Martinez LR
甲基苯丙胺（冰毒）是一种强效且极易上瘾的兴奋剂，影响美国和世界各地使用者的中枢神经系统，其消费与获得艾滋病毒和艾滋病相关感染有关。甲基苯丙胺增强小鼠隐球菌病，这是一种由被包裹的新型隐球菌真菌引起的机会性感染。由于其在巨噬细胞内存活的能力，新形态C.是研究病原体-巨噬细胞相互作用的理想模型。甲基苯丙胺破坏了正常的巨噬细胞功能，这可能导致吸毒者感染的发生率更高，进展更快。因此，我们研究了补体和针对新生C.荚膜多糖的特异性IgM对甲基苯丙胺暴露后J774.16巨噬细胞样细胞功能的影响。我们发现，与单独与补体共孵育相比，补体和IgM显著促进了J774.16细胞对补体介导的新生C.的吞噬。IgM可增强经药物处理的巨噬细胞表面补体受体3的表达。此外，igm增加的巨噬细胞吞噬可能与GTPase-RhoA的上调有关，GTPase-RhoA是肌动蛋白聚合信号级联的关键调节因子。与补体和IgM孵育的真菌细胞在甲基安非他明存在下显示出更高的细胞数量，这可能解释了它们被吞噬细胞增加的原因。IgM通过抑制吞噬体的碱化和刺激细胞内一氧化氮的产生，增加了巨噬细胞对酵母细胞的杀伤作用。总之，我们的研究结果表明，在药物滥用的情况下，IgM刺激巨噬细胞对机会性病原体的效应功能。
Methamphetamine (METH) is a powerful and highly addictive stimulant that affects the central nervous system of users in the United States and worldwide, and its consumption is associated to the acquisition of HIV and AIDS-related infections. METH enhances cryptococcosis in mice, an opportunistic infection caused by the encapsulated fungus Cryptococcus neoformans. Due to its ability to survive within macrophages, C. neoformans is an ideal model to study pathogen-macrophage interactions. METH abrogates normal macrophage function, which might contribute to the higher rate and more rapid progression of infections in drug abusers. Hence, we investigated the role of complement and specific IgM to C. neoformans capsular polysaccharide on the function of J774.16 macrophage-like cells after exposure to METH. We found that complement and IgM significantly promotes complement-mediated phagocytosis of C. neoformans by J774.16 cells in comparison to co-incubation with complement alone. IgM enhances the expression of complement receptor 3 on the surface macrophages treated with the drug. Also, IgM-increased macrophage phagocytosis of C. neoformans may be associated with upregulation of GTPase-RhoA, a key regulator of the actin polymerization signaling cascade. Fungal cells incubated with complement and IgM in the presence of METH demonstrated higher number of cells per aggregate, a possible explanation for their enhanced ingestion by phagocytes. IgM increased killing of yeast cells by macrophages by inhibiting the alkalization of the phagosome and stimulating the intracellular production of nitric oxide. Together, our findings suggest that IgM stimulates the effector functions of macrophages against opportunistic pathogens in the setting of drug abuse.
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影响因子：
12.7
作者：
Pevzner, Eric S.;Robison, Susan;Oeltmann, John E.
通讯作者：
Oeltmann, John E.
影响因子：
3.1
作者：
Feldmesser, M;Kress, Y;Casadevall, A
通讯作者：
Casadevall, A
影响因子：
3.8
作者：
Park, Benjamin J.;Wannemuehler, Kathleen A.;Chiller, Tom A.
通讯作者：
Chiller, Tom A.
影响因子：
2.8
作者：
Peerzada H;Gandhi JA;Guimaraes AJ;Nosanchuk JD;Martinez LR
通讯作者：
Martinez LR
影响因子：
6.4
作者：
Ellis, RJ;Childers, ME;Grant, I
通讯作者：
Grant, I