CD200 Modulates S. aureus-Induced Innate Immune Responses Through Suppressing p38 Signaling

Abstract

Rapid activation of macrophages plays a central role in eliminating invading bacteria as well as in triggering the inflammatory responses, but how the anti-bacterial and the inflammatory responses are coordinated, in terms of macrophages, is not completely understood. In this study, we demonstrated that Staphylococcus aureus (S. aureus) induced the expression of CD200 in murine macrophages in a dose-dependent manner. We found that CD200 significantly suppressed the S. aureus-induced production of nitric oxide and proinflammatory cytokines in mouse macrophages. Concurrently, the bactericidal capability of macrophages was boosted upon the deletion of CD200. Furthermore, our data demonstrated that p38 mitogen-activated protein kinase (MAPK) was selectively down-regulated by CD200 administration, while enhanced upon CD200 silence in response to staphylococcal infection. The negative effect of CD200 siRNA on NO production in macrophages was largely abrogated upon the inhibition of p38 signaling, implying its critical involvement in this regulation. Together, our data demonstrate that CD200 plays a central role in regulating the inflammatory responses and the anti-bacterial activity of macrophages, at least partially, through suppressing p38 activity.