Intrinsic antibody-dependent enhancement of microbial infection in macrophages: disease regulation by immune complexes.
Intrinsic antibody-dependent enhancement of microbial infection in macrophages: disease regulation by immune complexes.
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DOI：
10.1016/s1473-3099(10)70166-3
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发表时间：
2010-10
期刊：
影响因子：
--
通讯作者：
Mosser DM
中科院分区：
文献类型：
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作者：
Halstead SB;Mahalingam S;Marovich MA;Ubol S;Mosser DM
多种微生物可在巨噬细胞中复制，这些病原体通过非中和IgG抗体复合物进入细胞可通过特异质Fcγ受体信号传导导致细胞内感染增加。Fcγ受体的激活通常导致吞噬作用。特异性地，IgG免疫复合物连接单核细胞或巨噬细胞Fcγ受体，而不是帮助宿主防御，可以抑制先天免疫，增加白细胞介素10的产生，并使辅助性T细胞1（Th1）应答偏向Th2应答，导致感染细胞的感染输出增加。感染的这种内在抗体依赖性增强（ADE）调节了登革出血热和利什曼病等完全不同的疾病的严重程度。内源性ADE与外源性ADE不同，其中感染因子与非中和抗体的复合物导致感染细胞数量增加。内源性ADE可能参与许多原生动物、细菌和病毒感染。我们回顾了感染性免疫复合物连接巨噬细胞Fcγ受体后增强发病机制的细胞内机制和意义。
A wide range of microorganisms can replicate in macrophages, and cell entry of these pathogens via non-neutralising IgG antibody complexes can result in increased intracellular infection through idiosyncratic Fcγ-receptor signalling. The activation of Fcγ receptors usually leads to phagocytosis. Paradoxically, the ligation of monocyte or macrophage Fcγ receptors by IgG immune complexes, rather than aiding host defences, can suppress innate immunity, increase production of interleukin 10, and bias T-helper-1 (Th1) responses to Th2 responses, leading to increased infectious output by infected cells. This intrinsic antibody-dependent enhancement (ADE) of infection modulates the severity of diseases as disparate as dengue haemorrhagic fever and leishmaniasis. Intrinsic ADE is distinct from extrinsic ADE, whereby complexes of infectious agents with non-neutralising antibodies lead to an increased number of infected cells. Intrinsic ADE might be involved in many protozoan, bacterial, and viral infections. We review insights into intracellular mechanisms and implications of enhanced pathogenesis after ligation of macrophage Fcγ receptors by infectious immune complexes.