Hofbauer Cells Spread Listeria monocytogenes among Placental Cells and Undergo Pro-Inflammatory Reprogramming while Retaining Production of Tolerogenic Factors.
Hofbauer Cells Spread Listeria monocytogenes among Placental Cells and Undergo Pro-Inflammatory Reprogramming while Retaining Production of Tolerogenic Factors.
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DOI：
10.1128/mbio.01849-21
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发表时间：
2021-08-31
期刊：
影响因子：
6.4
通讯作者：
Seveau S
中科院分区：
文献类型：
--
作者：
Azari S;Johnson LJ;Webb A;Kozlowski SM;Zhang X;Rood K;Amer A;Seveau S
孕妇极易受到细菌病原体单核细胞增生李斯特菌的感染，导致流产、早产和新生儿感染。L.单核细胞增多症被认为通过感染母体/胎儿界面的滋养层而破坏胎盘屏障。然而，L.绒毛膜绒毛内的单核细胞增多症以及感染如何到达胎儿还没有确定。Hofbauer细胞（HBC）是胎儿胎盘巨噬细胞，也是唯一存在于健康绒毛膜绒毛中的白细胞，形成保护胎儿血液免受感染的最后一个免疫屏障。关于HBCs对病原体的抗菌反应知之甚少。在这里，我们研究了L。单核细胞增多症与人原发性HBCs的相互作用。值得注意的是，尽管它们在基础状态下具有M2抗炎表型，但HBCs吞噬并杀死非致病性细菌如无害李斯特菌，并显示出对李斯特菌感染的低易感性。单核细胞增多症然而，L.单核细胞增多症可以利用HBC扩散到周围的胎盘细胞。通过RNA测序的转录组学分析显示，HBCs在L.单核细胞增多症感染，类似于由有效的M1-极化剂脂多糖（LPS）/干扰素γ（IFN-γ）刺激的巨噬细胞。感染的HBCs还表达促炎趋化因子，已知其促进母体白细胞的胎盘浸润。然而，HBC维持致耐受性基因集合的表达和致耐受性细胞因子的分泌，这与它们在预防胎儿排斥中的组织稳态作用一致。总之，我们提出了一个以前未被认识的模型，其中HBCs促进L的传播。在胎盘细胞中的单核细胞增多症和转变到促炎状态可能有利于先天免疫应答，同时维持已知防止母体抗胎儿适应性免疫的致耐受性因子的表达。
Pregnant women are highly susceptible to infection by the bacterial pathogen Listeria monocytogenes, leading to miscarriage, premature birth, and neonatal infection. L. monocytogenes is thought to breach the placental barrier by infecting trophoblasts at the maternal/fetal interface. However, the fate of L. monocytogenes within chorionic villi and how infection reaches the fetus are unsettled. Hofbauer cells (HBCs) are fetal placental macrophages and the only leukocytes residing in healthy chorionic villi, forming a last immune barrier protecting fetal blood from infection. Little is known about the HBCs’ antimicrobial responses to pathogens. Here, we studied L. monocytogenes interaction with human primary HBCs. Remarkably, despite their M2 anti-inflammatory phenotype at basal state, HBCs phagocytose and kill non-pathogenic bacteria like Listeria innocua and display low susceptibility to infection by L. monocytogenes. However, L. monocytogenes can exploit HBCs to spread to surrounding placental cells. Transcriptomic analyses by RNA sequencing revealed that HBCs undergo pro-inflammatory reprogramming upon L. monocytogenes infection, similarly to macrophages stimulated by the potent M1-polarizing agents lipopolysaccharide (LPS)/interferon gamma (IFN-γ). Infected HBCs also express pro-inflammatory chemokines known to promote placental infiltration by maternal leukocytes. However, HBCs maintain the expression of a collection of tolerogenic genes and secretion of tolerogenic cytokines, consistent with their tissue homeostatic role in prevention of fetal rejection. In conclusion, we propose a previously unrecognized model in which HBCs promote the spreading of L. monocytogenes among placental cells and transition to a pro-inflammatory state likely to favor innate immune responses, while maintaining the expression of tolerogenic factors known to prevent maternal anti-fetal adaptive immunity.