The receptor for the complement C3a anaphylatoxin (C3aR) provides host protection against Listeria monocytogenes-induced apoptosis.
The receptor for the complement C3a anaphylatoxin (C3aR) provides host protection against Listeria monocytogenes-induced apoptosis.
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DOI：
10.4049/jimmunol.1302787
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发表时间：
2014-08-01
期刊：
影响因子：
--
通讯作者：
Wetsel RA
中科院分区：
文献类型：
--
作者：
Mueller-Ortiz SL;Morales JE;Wetsel RA
单核细胞增生李斯特菌（LM）是一种革兰氏阳性细胞内细菌，通过受污染的食物获得，可导致全身感染和可能的死亡。尽管先天免疫系统在对抗LM感染中的重要性，但对补体及其活化产物（包括强效C3 a过敏毒素）的作用知之甚少。在系统性LM感染的模型中，我们在这里表明，与WT小鼠相比，缺乏C3 a受体（C3 aR-/-）的小鼠对感染明显更敏感，表现为存活率降低，细菌负荷增加，肝脏和脾脏损伤增加。C3 aR-/-小鼠无法清除细菌感染不是由缺陷性巨噬细胞或已知在宿主对LM的应答中至关重要的细胞因子/趋化因子（包括IFN-γ和TNF-α）减少引起的。相反，TUNEL染色以及Fas、活性半胱天冬酶-3和Bcl-2表达数据表明，C3 aR-/-小鼠对LM感染的易感性增加主要是由LM诱导的脾中骨髓和淋巴细胞凋亡增加引起的，这些细胞是最终清除LM所需的，包括中性粒细胞、巨噬细胞、树突状细胞和T细胞。这些发现揭示了宿主免疫应答过程中C3 a/C3 aR信号传导的意想不到的功能，其抑制Fas表达和半胱天冬酶-3活性，同时增加Bcl-2表达，从而为骨髓和淋巴细胞提供保护以对抗LM诱导的凋亡。
Listeria monocytogenes (LM) is a Gram-positive intracellular bacterium that is acquired through tainted food and may lead to systemic infection and possible death. Despite the importance of the innate immune system in fighting LM infection, little is known about the role of complement and its activation products, including the potent C3a anaphylatoxin. In a model of systemic LM infection, we show here that mice lacking the receptor for C3a (C3aR-/-) are significantly more sensitive to infection compared to WT mice as demonstrated by decreased survival, increased bacterial burden, and increased damage to their livers and spleens. The inability of the C3aR-/- mice to clear the bacterial infection was not caused by defective macrophages or by reduction of cytokines/chemokines known to be critical in the host response to LM, including IFN-γ and TNF-α. Instead, TUNEL staining together with Fas, active caspase-3, and Bcl-2 expression data indicate that the increased susceptibility of C3aR-/- mice to LM infection was largely caused by increased LM-induced apoptosis of myeloid and lymphoid cells in the spleen that are required for ultimate clearance of LM, including neutrophils, macrophages, dendritic cells, and T cells. These findings reveal an unexpected function of C3a/C3aR signaling during the host immune response that suppresses Fas expression and caspase-3 activity while increasing Bcl-2 expression, thereby providing protection to both myeloid and lymphoid cells against LM-induced apoptosis.
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影响因子：
64.5
作者：
Joseph, SB;Bradley, MN;Tontonoz, P
通讯作者：
Tontonoz, P
影响因子：
32.4
作者：
HARTY, JT;BEVAN, MJ
通讯作者：
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DOI：
10.4049/jimmunol.1102341
发表时间：
2012-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
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通讯作者：
Berg RE
影响因子：
15.3
作者：
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通讯作者：
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影响因子：
56.9
作者：
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通讯作者：
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