Differential spleen immune signatures and germinal center responses during acute infection with

Introduction: Scrub typhus is an emerging and neglected tropical disease caused by Methods: We 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. Results: Karp 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. On day 4 post-infection, Karp induced significant elevation of transcriptional inflammatory signatures ( Discussion: Collectively, this study provides the first lines of evidence for Ot strain-related, cellular and humoral immune signatures in the spleens, which help understand differential host immune responses during acute scrub typhus.