ABSTRACT

Scavenger receptors are part of a complex surveillance system expressed by host cells to efficiently orchestrate innate immune response against bacterial infections. Stabilin-1 (STAB-1) is a scavenger receptor involved in cell trafficking, inflammation, and cancer; however, its role in infection remains to be elucidated. Listeria monocytogenes (Lm) is a major intracellular human food-borne pathogen causing severe infections in susceptible hosts. Using a mouse model of infection, we demonstrate here that STAB-1 controls Lm-induced cytokine and chemokine production and immune cell accumulation in Lm-infected organs. We show that STAB-1 also regulates the recruitment of myeloid cells in response to Lm infection and contributes to clear circulating bacteria. In addition, whereas STAB-1 appears to promote bacterial uptake by macrophages, infection by pathogenic Listeria induces the down regulation of STAB-1 expression and its delocalization from the host cell membrane.

We propose STAB-1 as a new SR involved in the control of Lm infection through the regulation of host defense mechanisms, a process that would be targeted by bacterial virulence factors to promote infection.

摘要

清道夫受体是宿主细胞表达的复杂监视系统的一部分，可有效协调针对细菌感染的先天免疫反应。Stabilin-1 (STAB-1) 是一种清道夫受体，参与细胞运输、炎症和癌症；然而，它在感染中的作用仍有待阐明。单核细胞增生李斯特菌( Lm ) 是一种主要的细胞内人类食源性病原体，可在易感宿主中引起严重感染。使用感染的小鼠模型，我们在此证明 STAB-1 控制Lm诱导的细胞因子和趋化因子的产生以及Lm感染的器官中的免疫细胞积累。我们表明，STAB-1 还调节骨髓细胞的募集以响应Lm感染并有助于清除循环细菌。此外，虽然 STAB-1 似乎促进了巨噬细胞对细菌的摄取，但致病性李斯特菌的感染诱导了 STAB-1 表达的下调及其从宿主细胞膜的离域。

我们建议将 STAB-1 作为一种新的 SR，通过调节宿主防御机制参与控制Lm感染，这一过程将被细菌毒力因子靶向以促进感染。