Differential spleen immune signatures and germinal center responses during acute infection with Orientia tsutsugamushi Karp versus Gilliam strains

IntroductionScrub typhus is an emerging and neglected tropical disease caused by Orientia tsutsugamushi (Ot). Immunity in scrub typhus patients is known to be short-lived; however, its underlying mechanisms remain unclear.

No reports have examined humoral immune signatures to clinically prevalent Ot strains.MethodsWe compared two clinically relevant Ot strains, Karp and Gilliam, in a C57BL/6 murine model. Using equivalent infectious doses, we assessed splenic B cell and germinal center (GC) responses during acute infection through flow cytometry, immunohistology, serological analyses, and RNA sequencing.ResultsKarp infection resulted in high tissue bacterium burdens and 50% mortality rates, whereas Gilliam infection was self-healing with limited bacterium dissemination and growth.

Yet, Gilliam induced strong splenic B cell responses, as judged by total numbers of B cells, follicular B cells, and marginal zone B cells, which correlated with serum IgG and IgM levels. Given that Karp- but not Gilliam-infected spleens displayed GC disorganization/loss and MZ abrogation, we compared splenic RNAseq profiles.