Anaphylatoxin signaling activates macrophages to control intracellular Rickettsia proliferation.
Anaphylatoxin signaling activates macrophages to control intracellular Rickettsia proliferation.
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DOI：
10.1128/spectrum.02538-23
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发表时间：
2023-12-12
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
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致病性立克次体物种在体内在容许宿主细胞的细胞质内增殖。这些宿主细胞的细胞质足以支持立克次体生长的复杂代谢和生理需求。然而，当立克次氏体遇到先天免疫细胞时，宿主/病原体之间会发生戏剧性的相互作用，从而细菌可以正常增殖，或者宿主可以限制细菌生长。这种相互作用在髓样宿主细胞中最为不同，其中细胞内和细胞外因子可以产生成功的立克次体寄生或细菌增殖的先天免疫控制。有了哺乳动物补体系统在哺乳动物感染过程中被激活的先验知识，我们试图确定细胞外补体激活和过敏毒素信号传导是否可以改变单核宿主细胞内立克次体的命运。结果表明，生长培养基中补充C3 a或C5 a过敏毒素肽足以使许多骨髓细胞控制多种不同立克次体物种的增殖。过敏毒素信号传导或过敏毒素受体的化学或遗传破坏消除了补体诱导的细菌增殖限制。最后，过敏毒素信号通过诱导最终控制这些病原体的细胞内增殖的炎性表型来改变巨噬细胞生理学。致病性立克次体是一种非常危险的细菌，生长在宿主哺乳动物细胞的细胞质中。在大多数情况下，这些细菌能够压倒宿主细胞，并在细胞质的保护环境中生长。然而，当立克次体遇到先天免疫细胞时，会发生戏剧性的冲突;细菌可以通过接管宿主而“获胜”，或者如果宿主细胞有效地对抗感染，细菌可能会“失败”。这份手稿研究了免疫补体系统如何能够检测立克次体的存在并警告附近的细胞。补体激活的副产物称为过敏毒素，是“激活”先天免疫细胞以启动攻击性防御策略的信号。这项研究增强了我们对细胞内细菌先天免疫反应的集体理解，并将有助于未来控制这些危险感染的努力。
Pathogenic Rickettsia species proliferate within the cytoplasm of permissive host cells in vivo. The cytoplasm of these host cells is adequate to support the complex metabolic and physiological needs for Rickettsia growth. However, a dramatic host/pathogen interplay occurs when Rickettsia encounter innate immune cells, whereby the bacteria can proliferate as normal or the host can restrict bacterial growth. This interplay is most divergent within myeloid host cells, where intra- and extracellular factors can produce either successful Rickettsia parasitism or innate immune control of bacterial proliferation. With the prior knowledge that the mammalian complement system is activated during mammalian infection, we sought to determine if extracellular complement activation and anaphylatoxin signaling can modify the fate of Rickettsia within mononuclear host cells. Results indicate that supplementation of growth media with either C3a or C5a anaphylatoxin peptides is sufficient for many myeloid cells to control the proliferation of multiple different Rickettsia species. Chemical or genetic disruption of anaphylatoxin signaling or anaphylatoxin receptors eliminates complement-induced restriction of bacterial proliferation. Finally, anaphylatoxin signaling modifies macrophage physiology by inducing inflammatory phenotypes that ultimately control the intracellular proliferation of these pathogens. Pathogenic Rickettsia species are extremely dangerous bacteria that grow within the cytoplasm of host mammalian cells. In most cases, these bacteria are able to overpower the host cell and grow within the protected environment of the cytoplasm. However, a dramatic conflict occurs when Rickettsia encounter innate immune cells; the bacteria can “win” by taking over the host, or the bacteria can “lose” if the host cell efficiently fights the infection. This manuscript examines how the immune complement system is able to detect the presence of Rickettsia and alert nearby cells. Byproducts of complement activation called anaphylatoxins are signals that “activate” innate immune cells to mount an aggressive defensive strategy. This study enhances our collective understanding of the innate immune reaction to intracellular bacteria and will contribute to future efforts at controlling these dangerous infections.
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DOI：
10.4049/jimmunol.1302787
发表时间：
2014-08-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Mueller-Ortiz SL;Morales JE;Wetsel RA
通讯作者：
Wetsel RA
影响因子：
3.6
作者：
Dahmani M;Cook JH;Zhu JC;Riley SP
通讯作者：
Riley SP
影响因子：
3.7
作者：
Subramanian H;Gupta K;Ali H
通讯作者：
Ali H
影响因子：
3.1
作者：
Bechelli, Jeremy;Smalley, Claire;Fang, Rong
通讯作者：
Fang, Rong
DOI：
10.3390/pathogens10020228
发表时间：
2021-02-19
期刊：
Pathogens (Basel, Switzerland)
影响因子：
--
作者：
Kristof MN;Allen PE;Yutzy LD;Thibodaux B;Paddock CD;Martinez JJ
通讯作者：
Martinez JJ