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bioRxiv · 10.1101/2024.05.10.593542

Pathogenic rickettsiae utilize the phosphatidylserine binding receptor CD300f on macrophages for host invasion and pathogenesis.

Voss, O. H.·Moin, I.·Gaytan, H.·Ullah, S.·Sadik, M.·Azad, A. F.·Rahman, M. S.
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Abstract

Some arthropod-borne obligate intracellular rickettsiae are among the most virulent human pathogens. Rickettsia species modulate immune (e.g., macrophages; M{Phi}) and non-immune cell (e.g., endothelial cells) responses to create a habitable environment for host colonization. In particular, M{Phi} play a crucial role in either terminating an infection at an early stage or succumbing to bacterial replication and colonization. However, our understanding on how Rickettsia species invade host cells, including M{Phi}, remain 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 M{Phi}. Using bone marrow-derived macrophages (BMDM{Phi}) from wild-type (WT) and CD300f-/- mice, we demonstrated that engulfment of both pathogenic R. typhi (the etiologic agent of murine typhus) and R. rickettsii (the etiologic agent of Rocky Mountain spotted fever) species as well as the non-pathogenic R. montanensis was significantly reduced in CD300f-/- BMDM{Phi} as compared to that of WT BMDM{Phi}. Furthermore, our mechanistic analysis suggests bacterial PS as the potential source for the CD300f-mediated rickettsiae engulfment by M{Phi}. In vivo infection studies using WT and CD300f-/- C57BL/6J mice showed that CD300f-/- animals were protected against R. typhi-or R. rickettsii-induced fatal rickettsiosis, which correlated with levels of bacterial burden detected in the spleens of mice. Adoptive transfer studies further revealed that CD300f-expressing M{Phi} 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.

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Voss, O. H., Moin, I., Gaytan, H., Ullah, S., Sadik, M., Azad, A. F., Rahman, M. S.. 2024-05-10. Pathogenic rickettsiae utilize the phosphatidylserine binding receptor CD300f on macrophages for host invasion and pathogenesis.. https://doi.org/10.1101/2024.05.10.593542

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