{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:49:24Z","timestamp":1790668164226,"version":"4.1.0"},"posted":{"date-parts":[[2025,6,30]]},"group-title":"Immunology","reference-count":65,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["P20-GM103625"],"award-info":[{"award-number":["P20-GM103625"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]},{"award":["TR003109"],"award-info":[{"award-number":["TR003109"]}],"id":[{"id":"https:\/\/ror.org\/04pw6fb54","id-type":"ROR","asserted-by":"publisher"}]},{"award":["UL1 TR003107"],"award-info":[{"award-number":["UL1 TR003107"]}],"id":[{"id":"https:\/\/ror.org\/04pw6fb54","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Cutaneous leishmaniasis (CL) is a debilitating neglected tropical disease characterized by lesions that can range from self-healing to permanent disfigurations. A predominant Th1 response, which stimulates IFN-\u03b3 production, is crucial for parasite control during self-healing CL. While IFN-\u03b3 primarily activates macrophages to produce nitric oxide via inducible nitric oxide synthase (iNOS) leading to parasite control, IFN-\u03b3 also activates other downstream pathways involved in cell autonomous immunity. One such pathway is the activation of guanylate binding proteins (GBPs), a class of interferon inducible GTPases. However, the role of GBPs during CL has been minimally explored. Utilizing RNA-Seq we found that\n                  <jats:italic>Leishmania major<\/jats:italic>\n                  infection leads to the upregulation of several GBPs in C57Bl\/6 mice. In vitro studies using GBPChr3 knockout (KO), and C57Bl\/6 control mice reveal that bone marrow-derived macrophages (BMDMs) from KO mice exhibit higher parasite burdens following IFN-\u03b3 treatment, independent of GBP localization to the parasite. Single-cell RNA-Seq identifies macrophages as the primary expressers of GBPs during\n                  <jats:italic>L. major<\/jats:italic>\n                  infection\n                  <jats:italic>in vivo<\/jats:italic>\n                  .\n                  <jats:italic>In vivo<\/jats:italic>\n                  , GBPChr3 KO mice display increased disease severity and parasite load. GBPChr3 KO macrophages and monocytes show elevated ARG-1 and reduced iNOS expression, indicating a shift toward a parasite-permissive environment that supports parasite growth. These findings highlight a critical role for GBPs in immune-mediated control of CL.\n                <\/jats:p>","DOI":"10.1101\/2025.06.26.661809","type":"posted-content","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:45:15Z","timestamp":1751330715000},"source":"Crossref","is-referenced-by-count":0,"title":["Guanylate-Binding Proteins Promote Host Defense Against\n                  <i>Leishmania major<\/i>\n                  by Balancing iNOS\/Arg-1 in Myeloid Cells"],"prefix":"10.64898","author":[{"given":"Lucy","family":"Fry","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Het","family":"Adhvaryu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayden","family":"Roys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Bowlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gopinath","family":"Venugopal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan T.","family":"Bird","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charity","family":"Washam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rn","family":"Coers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Byrum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Voth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Weinkopff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025070217251414000_2025.06.26.661809v1.1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.11120.1"},{"key":"2025070217251414000_2025.06.26.661809v1.2","doi-asserted-by":"publisher","DOI":"10.1590\/0074-02760160138"},{"key":"2025070217251414000_2025.06.26.661809v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cimid.2004.03.004"},{"key":"2025070217251414000_2025.06.26.661809v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.72"},{"key":"2025070217251414000_2025.06.26.661809v1.5","doi-asserted-by":"crossref","unstructured":"Volpedo G , Pacheco-Fernandez T , Holcomb EA , Cipriano N , Cox B , Satoskar AR . 2021. 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