Complement modulates the cutaneous microbiome and inflammatory milieu

被引:126
作者
Chehoud, Christel [1 ]
Rafail, Stavros [2 ]
Tyldsley, Amanda S. [1 ]
Seykora, John T. [1 ]
Lambris, John D. [2 ]
Grice, Elizabeth A. [1 ]
机构
[1] Univ Penn, Dept Dermatol, Perelman Sch Med, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA
关键词
HUMAN SKIN; IMMUNE-RESPONSE; DIVERSITY; PSORIASIS; DEFICIENCY; EXPRESSION; CHILDREN; RECEPTOR; SCALES; SHIFTS;
D O I
10.1073/pnas.1307855110
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:15061 / 15066
页数:6
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