AUTHOR=Kumaresan Venkatesh , Ingle Taylor MacMackin , Kilgore Nathan , Zhang Guoquan , Hermann Brian P. , Seshu Janakiram 

TITLE=Cellular and transcriptome signatures unveiled by single-cell RNA-Seq following ex vivo infection of murine splenocytes with Borrelia burgdorferi

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1296580

DOI=10.3389/fimmu.2023.1296580

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>Lyme disease, the most common tick-borne infectious disease in the US, is caused by a spirochetal pathogen <italic>Borrelia burgdorferi</italic> (<italic>Bb</italic>). Distinct host responses are observed in susceptible and resistant strains of inbred of mice following infection with <italic>Bb</italic> reflecting a subset of inflammatory responses observed in human Lyme disease. The advent of post-genomic methodologies and genomic data sets enables dissecting the host responses to advance therapeutic options for limiting the pathogen transmission and/or treatment of Lyme disease.</p></sec><sec><title>Methods</title><p>In this study, we used single-cell RNA-Seq analysis in conjunction with mouse genomics exploiting GFP-expressing <italic>Bb</italic> to sort GFP+ splenocytes and GFP− bystander cells to uncover novel molecular and cellular signatures that contribute to early stages of immune responses against <italic>Bb</italic>.</p></sec><sec><title>Results</title><p>These data decoded the heterogeneity of splenic neutrophils, macrophages, NK cells, B cells, and T cells in C3H/HeN mice in response to <italic>Bb</italic> infection. Increased mRNA abundance of apoptosis-related genes was observed in neutrophils and macrophages clustered from GFP+ splenocytes. Moreover, complement-mediated phagocytosis-related genes such as C1q and Ficolin were elevated in an inflammatory macrophage subset, suggesting upregulation of these genes during the interaction of macrophages with <italic>Bb</italic>-infected neutrophils. In addition, the role of DUSP1 in regulating the expression of Casp3 and pro-inflammatory cytokines Cxcl1, Cxcl2, Il1b, and Ccl5 in <italic>Bb</italic>-infected neutrophils were identified.</p></sec><sec><title>Discussion</title><p>These findings serve as a growing catalog of cell phenotypes/biomarkers among murine splenocytes that can be exploited for limiting spirochetal burden to limit the transmission of the agent of Lyme disease to humans via reservoir hosts.</p></sec>