Complement modulates the cutaneous microbiome and inflammatory milieu
Complement modulates the cutaneous microbiome and inflammatory milieu
复制标题
DOI：
10.1073/pnas.1307855110
复制
发表时间：
2013-09-10
影响因子：
11.1
通讯作者：
Grice, Elizabeth A.
中科院分区：
文献类型：
--
作者：
Chehoud, Christel;Rafail, Stavros;Grice, Elizabeth A.
皮肤被包括共生菌和潜在病原体在内的大量微生物定植，但目前尚不清楚皮肤宿主免疫机制如何影响皮肤微生物区系的组成、多样性和数量。在这里，我们揭示了补体在皮肤宿主-微生物群相互作用中的交互作用。细菌16S rRNA基因的深度测序显示，抑制补体成分C5a受体(C5aR)的信号转导改变了皮肤微生物区系的组成和多样性。同时，我们证明C5aR抑制导致编码皮肤抗菌肽、模式识别受体和促炎介质的基因下调。免疫组织化学显示皮肤炎症细胞浸润减少，巨噬细胞和淋巴细胞数量减少，C5aR受到抑制。此外，比较无菌小鼠和常规饲养小鼠的皮肤基因表达表明，共生微生物群调节皮肤中补体基因的表达。这些发现证明了宿主免疫的一个组成部分，它影响共生微生物群对皮肤的定植，反之亦然，这是了解皮肤的宿主-微生物免疫互惠关系及其对健康和疾病的影响的关键一步。此外，我们揭示了补体在皮肤的动态平衡宿主-微生物群相互作用中的作用。
The skin is colonized by a plethora of microbes that include commensals and potential pathogens, but it is currently unknown how cutaneous host immune mechanisms influence the composition, diversity, and quantity of the skin microbiota. Here we reveal an interactive role for complement in cutaneous host-microbiome interactions. Inhibiting signaling of the complement component C5a receptor (C5aR) altered the composition and diversity of the skin microbiota as revealed by deep sequencing of the bacterial 16S rRNA gene. In parallel, we demonstrate that C5aR inhibition results in down-regulation of genes encoding cutaneous antimicrobial peptides, pattern recognition receptors, and proinflammatory mediators. Immunohistochemistry of inflammatory cell infiltrates in the skin showed reduced numbers of macrophages and lymphocytes with C5aR inhibition. Further, comparing cutaneous gene expression in germ-free mice vs. conventionally raised mice suggests that the commensal microbiota regulates expression of complement genes in the skin. These findings demonstrate a component of host immunity that impacts colonization of the skin by the commensal microbiota and vice versa, a critical step toward understanding host-microbe immune mutualism of the skin and its implications for health and disease. Additionally, we reveal a role for complement in homeostatic host-microbiome interactions of the skin.