Investigation on the role of specific myeloid subset influenced by microbiota against skin infection

Abstract

Microbiota is essential in development and functional maturation of our immune system, even outside the gut. However, whether and how gut microbiota may affect skin myeloid cells is unclear. Present study presents a microbiota-dependent macrophage subset that aid in protection against skin infection. I found evident downregulation of type I interferon signaling in skin of germ free mice compared to specific pathogen free mice. The decrease in type I interferon signaling was closely related to microbiota presence and a macrophage-specific marker Siglec-1 (CD169). CD169 expression was inducible using recombinant type I interferons in bone marrow-derived macrophages. Absence of CD169$^+$ macrophages resulted in increased bacterial burden and impairment of immune response against S. aureus skin infection. CD169$^+$ macrophages mediated not only recruitment of neutrophil and γδ T cells, but also activation of γδ T cells via IL-23. Absence of CD169$^+$ macrophages lead to diminished number of IL-17 producing T cells, which are essential for host defense against S. aureus. My findings verify a role of microbiota in establishment of a specific myeloid cell subset expressing CD169 in the skin and provide specific mechanism of how the subset protects against bacterial skin infection.