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Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Lyme disease, the most common tick-borne infectious disease in the US, is caused by a spirochetal pathogen <jats:italic>Borrelia burgdorferi<\/jats:italic> (<jats:italic>Bb<\/jats:italic>). Distinct host responses are observed in susceptible and resistant strains of inbred of mice following infection with <jats:italic>Bb<\/jats: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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we used single-cell RNA-Seq analysis in conjunction with mouse genomics exploiting GFP-expressing <jats:italic>Bb<\/jats:italic> to sort GFP+ splenocytes and GFP\u2212 bystander cells to uncover novel molecular and cellular signatures that contribute to early stages of immune responses against <jats:italic>Bb<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>These data decoded the heterogeneity of splenic neutrophils, macrophages, NK cells, B cells, and T cells in C3H\/HeN mice in response to <jats:italic>Bb<\/jats: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 <jats:italic>Bb<\/jats: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 <jats:italic>Bb<\/jats:italic>-infected neutrophils were identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats: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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1296580","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T12:27:14Z","timestamp":1702038434000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Cellular and transcriptome signatures unveiled by single-cell RNA-Seq following ex vivo infection of murine splenocytes with Borrelia burgdorferi"],"prefix":"10.3389","volume":"14","author":[{"given":"Venkatesh","family":"Kumaresan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor MacMackin","family":"Ingle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Kilgore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoquan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian 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