{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T07:19:52Z","timestamp":1776842392364,"version":"3.51.2"},"reference-count":152,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI152233 , R21AI149263"],"award-info":[{"award-number":["R01AI152233 , R21AI149263"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    <jats:italic>Borrelia burgdorferi (Bb)<\/jats:italic>\n                    , the spirochetal agent of Lyme disease, has a large array of lipoproteins that play a significant role in mediating host-pathogen interactions within ticks and vertebrates. While prior work has established that borrelial lipoproteins (\n                    <jats:italic>Bb<\/jats:italic>\n                    LP) modulate immune signaling pathways, the broader transcriptional and proteomic programs induced by these molecules in macrophages are unclear. Here, we used integrated multi-omics approaches to characterize host signaling pathways activated specifically by purified borrelial lipoproteins in murine bone marrow derived macrophages (BMDMs). Single-cell RNA-Seq (scRNA-Seq) performed on BMDMs treated with various concentrations of borrelial lipoproteins revealed macrophage subsets within the BMDMs. Differential expression analysis showed that genes encoding various receptors, type I IFN-stimulated genes, signaling chemokines are upregulated while mitochondrial and ribosomal genes are downregulated in BMDMs in response to lipoproteins. Unbiased proteomics analysis of lysates of BMDMs treated with lipoproteins corroborated several of these findings. Notably, dual specificity phosphatase 1 (\n                    <jats:italic>Dusp1<\/jats:italic>\n                    ) gene was upregulated during the early stages of BMDM exposure to\n                    <jats:italic>Bb<\/jats:italic>\n                    LP. Pharmacological inhibition with benzylidene-3-cyclohexylamino-1-indanone hydrochloride (BCI), an inhibitor of both DUSP1 and 6 prior to exposure to\n                    <jats:italic>Bb<\/jats:italic>\n                    LP, demonstrated that DUSP1 negatively regulates NLRP3-mediated pro-inflammatory signaling and positively regulates the expression of interferon-stimulated genes and those encoding\n                    <jats:italic>Ccl5<\/jats:italic>\n                    ,\n                    <jats:italic>Il1b<\/jats:italic>\n                    , and\n                    <jats:italic>Cd274<\/jats:italic>\n                    . Using human monocytic reporter cell lines, we showed MyD88- and IKK-dependent pathways contribute to mitochondrial alterations upon stimulation with lipoproteins. Extracellular flux analysis using the Seahorse assay revealed decreased oxygen consumption rate (OCR) and increased extracellular acidification rate (ECAR), indicating time-dependent metabolic reprogramming and a shift toward a glycolytic, pro-inflammatory metabolic state in BMDMs following\n                    <jats:italic>Bb<\/jats:italic>\n                    LP stimulation. Collectively, these findings define signaling networks, regulatory nodes and metabolic alterations induced by borrelial lipoproteins in macrophages and highlight DUSP1 as a key modulator of lipoprotein-driven innate immune responses. This work provides a mechanistic framework for understanding how borrelial lipoproteins shape macrophage signaling, independent of the broader complexity of infection with intact pathogen.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1766756","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T04:20:10Z","timestamp":1775535610000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Role of dual specificity phosphatase 1 in influencing inflammatory pathways in macrophages modulated by Borrelia burgdorferi lipoproteins"],"prefix":"10.3389","volume":"17","author":[{"given":"Venkatesh","family":"Kumaresan","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, South Texas Center for Emerging Infectious Diseases","place":["San Antonio, TX, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanta","family":"Pahari","sequence":"additional","affiliation":[{"name":"Host Pathogen Interactions Program, Texas Biomedical Research Institute","place":["San Antonio, TX, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiung-Yu","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, South Texas Center for Emerging Infectious Diseases","place":["San Antonio, TX, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian P.","family":"Hermann","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio","place":["San Antonio, TX, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry S.","family":"Schlesinger","sequence":"additional","affiliation":[{"name":"Host Pathogen Interactions Program, Texas Biomedical Research Institute","place":["San Antonio, TX, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Seshu","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, South Texas Center for Emerging Infectious Diseases","place":["San Antonio, TX, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3201\/eid2702.202731","article-title":"Estimating the frequency of Lyme disease diagnoses, United States, 2010-2018","volume":"27","author":"Kugeler","year":"2021","journal-title":"Emerg Infect Dis"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2714","article-title":"Lyme disease-a tick-borne 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