FPR1是宿主免疫细胞上的瘟疫受体,Nature

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FPR1是宿主免疫细胞上的瘟疫受体
Nature ( IF 50.5 ) Pub Date : 2019-09-18 , DOI: 10.1038/s41586-019-1570-z
Patrick Osei-Owusu _{1,

2} , Thomas M Charlton _{1,

2} , Hwan Keun Kim _{1,

2} , Dominique Missiakas _{1,

2} , Olaf Schneewind _{1,

2}

Affiliation

鼠疫病原体鼠疫耶尔森菌利用 III 型分泌系统选择性破坏人体免疫细胞，从而使鼠疫耶尔森氏菌在血液中繁殖并通过跳蚤传播给新宿主。导致鼠疫细菌选择性破坏免疫细胞的宿主因素尚不清楚。在这里，我们展示了鼠疫杆菌 III 型分泌系统的针帽蛋白 LcrV 与人类免疫细胞上的 N-甲酰肽受体 (FPR1) 结合以促进细菌效应物的易位。鼠疫感染的特点是死亡率高；然而，Fpr1 缺陷小鼠的存活率和抗体反应增加，可预防鼠疫。我们将 FPR1R190W 鉴定为人类的候选抗性等位基因，可保护中性粒细胞免受 Y. 鼠疫III型分泌系统。因此，FPR1 是人类和小鼠免疫细胞上的瘟疫受体，它的缺失或突变提供了对抗鼠疫杆菌的保护。此外，FPR1 等位基因的瘟疫选择似乎塑造了人类对其他传染病和恶性肿瘤的免疫反应。人类免疫细胞上的受体 FPR1 与鼠疫杆菌相互作用，该受体的突变提供了人类对瘟疫的抵抗力，Fpr1 缺乏可提高在老鼠。

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FPR1 is the plague receptor on host immune cells

The causative agent of plague, Yersinia pestis, uses a type III secretion system to selectively destroy immune cells in humans, thus enabling Y. pestis to reproduce in the bloodstream and be transmitted to new hosts through fleabites. The host factors that are responsible for the selective destruction of immune cells by plague bacteria are unknown. Here we show that LcrV, the needle cap protein of the Y. pestis type III secretion system, binds to the N-formylpeptide receptor (FPR1) on human immune cells to promote the translocation of bacterial effectors. Plague infection in mice is characterized by high mortality; however, Fpr1-deficient mice have increased survival and antibody responses that are protective against plague. We identified FPR1R190W as a candidate resistance allele in humans that protects neutrophils from destruction by the Y. pestis type III secretion system. Thus, FPR1 is a plague receptor on immune cells in both humans and mice, and its absence or mutation provides protection against Y. pestis. Furthermore, plague selection of FPR1 alleles appears to have shaped human immune responses towards other infectious diseases and malignant neoplasms.The receptor FPR1 on human immune cells interacts with Yersinia pestis, mutations in this receptor provide resistance against plague in humans and Fpr1 deficiency enhances survival in mice.

更新日期：2019-09-18

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