Extracellular stimulation of VSIG4/complement receptor Ig suppresses intracellular bacterial infection by inducing autophagy
Extracellular stimulation of VSIG4/complement receptor Ig suppresses intracellular bacterial infection by inducing autophagy
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DOI：
10.1080/15548627.2016.1196314
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发表时间：
2016-01-01
期刊：
影响因子：
13.3
通讯作者：
Kwon, Byoung S.
中科院分区：
文献类型：
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作者：
Kim, Kwang H.;Choi, Beom K.;Kwon, Byoung S.
VSIG4/CRIG(V-SET和免疫球蛋白结构域包含4)是免疫球蛋白超家族的一种跨膜受体，特异性表达于巨噬细胞和成熟树突状细胞上。VSIG4信号可加速C3调理细菌的吞噬，从而有效清除巨噬细胞内的病原体。我们发现，由C3调理李斯特菌(OpLM)或激发型抗VSIG4单抗(MAb)触发的VSIG4信号可诱导巨噬细胞形成自噬。VSIG4诱导的自噬小体选择性地与细胞内的LM共定位，而饥饿诱导的自噬小体不能。与这些结果一致的是，在VSIG4缺陷的骨髓源性巨噬细胞(BMDM)中，由opLM感染诱导的自噬小体的频率低于WT BMDM。此外，当VSIG4分子在非巨噬细胞HeLa细胞中过表达时，VSIG4触发导致有效地摄取LM，形成自噬小体，并杀死受感染的LM。这些发现表明，VSIG4信号不仅像先前报道的那样促进C3调理的细胞内细菌的快速吞噬和杀灭，而且还诱导自噬小体的形成，消除从吞噬小体中逃逸的LM。我们得出结论，VSIG4信号提供了一种抗免疫逃避机制，防止巨噬细胞内细菌的生长。
VSIG4/CRIg (V-set and immunoglobulin domain containing 4) is a transmembrane receptor of the immunoglobulin superfamily that is expressed specifically on macrophages and mature dendritic cells. VSIG4 signaling accelerates phagocytosis of C3-opsonized bacteria, thereby efficiently clearing pathogens within macrophages. We found that VSIG4 signaling triggered by C3-opsonized Listeria (opLM) or by agonistic anti-VSIG4 monoclonal antibody (mAb) induced macrophages to form autophagosomes. VSIG4-induced autophagosomes were selectively colocalized with the intracellular LM while starvation-induced autophagosomes were not. Consistent with these results, the frequency of autophagosomes induced by infection with opLM was lower in VSIG4-deficient bone marrow-derived macrophages (BMDMs) than in WT BMDMs. Furthermore, when VSIG4 molecules were overexpressed in HeLa cells, which are non-macrophage cells, VSIG4 triggering led to efficient uptake of LM, autophagosome formation, and killing of the infected LM. These findings suggest that VSIG4 signaling not only promotes rapid phagocytosis and killing of C3-opsonized intracellular bacteria, as previously reported, but also induces autophagosome formation, eliminating the LM that have escaped from phagosomes. We conclude that VSIG4 signaling provides an anti-immune evasion mechanism that prevents the outgrowth of intracellular bacteria in macrophages.