Phosphatidylserine-binding receptor, CD300f, on macrophages mediates host invasion of pathogenic and non-pathogenic rickettsiae.

Some arthropod-borne obligate intracellular rickettsiae are among the most virulent human pathogens. Rickettsia species modulate immune (e.g., macrophages; MΦ) and non-immune cell (e.g., endothelial cells) responses to create a habitable environment for host colonization. MΦ play a crucial role in either terminating an infection at an early stage or succumbing to bacterial replication and colonization. However, our understanding of how Rickettsia species invade host cells, including MΦ, remains poorly defined. In this study, we describe a mechanism of host invasion by Rickettsia species, involving rickettsial phosphatidylserine (PS), as a ligand, and the CD300f receptor on MΦ. Our data reveal that engulfment of both pathogenic Rickettsia typhi (the etiologic agent of murine typhus) and Rickettsia rickettsii (the etiologic agent of Rocky Mountain spotted fever) species, as well as the non-pathogenic Rickettsia montanensis, is significantly reduced in bone marrow-derived macrophages (BMDMΦ) from CD300f^-/- mice, as compared to that of wild-type (WT) animals. Furthermore, our mechanistic analysis suggests bacterial PS as the potential source for the CD300f-mediated rickettsiae engulfment by MΦ. In vivo infection studies using WT and CD300f^-/- C57BL/6J mice show that CD300f^-/- animals are protected against R. typhi- or R. rickettsii-induced fatal rickettsiosis, which corroborates with the level of the bacterial burden detected in the spleens of the mice. Adoptive transfer studies reveal that CD300f-expressing MΦ are important mediators to control rickettsiosis in vivo. Collectively, our findings describe a previously unappreciated role for the efferocytic receptor, CD300f, to facilitate engulfment of rickettsiae within the host.