{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:13:08Z","timestamp":1785413588321,"version":"3.56.0"},"reference-count":66,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20-GM103625"],"award-info":[{"award-number":["P20-GM103625"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["TL1 TR003109, UL1 TR003107"],"award-info":[{"award-number":["TL1 TR003109, UL1 TR003107"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM106999"],"award-info":[{"award-number":["GM106999"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,4,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <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 disfiguration. 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, it 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 toggle=\"yes\">Leishmania major<\/jats:italic>\n                      infection leads to the upregulation of several Gbps in C57BL\/6 mice.\n                      <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                      studies using Gbp\n                      <jats:sup>Chr3<\/jats:sup>\n                      knockout (KO) and C57BL\/6 control mice reveal that bone marrow-derived macrophages 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 toggle=\"yes\">L. major<\/jats:italic>\n                      infection\n                      <jats:italic toggle=\"yes\">in vivo. In vivo<\/jats:italic>\n                      , Gbp\n                      <jats:sup>Chr3<\/jats:sup>\n                      KO mice display increased disease severity and parasite load. Gbp\n                      <jats:sup>Chr3<\/jats:sup>\n                      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>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Leishmania<\/jats:italic>\n                        parasites cause cutaneous lesions that are often resistant to drug treatment, and no vaccine is currently available, highlighting the need to better understand host mechanisms that control infection. In this manuscript, we explore the role of guanylate-binding proteins (Gbps) in host macrophages during\n                        <jats:italic toggle=\"yes\">Leishmania major<\/jats:italic>\n                        infection. We demonstrate that Gbps are critical for host defense both\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        and\n                        <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                        . Notably, this protection is independent of Gbp localization to the parasite, revealing a novel aspect of Gbp biology. Instead, we find that differences in parasite burden and disease severity in Gbp-deficient mice are linked to altered activation of tissue macrophages and monocytes. Our findings suggest that Gbps coordinate inducible nitric oxide synthase expression in macrophages, the primary cells that house and control\n                        <jats:italic toggle=\"yes\">Leishmania<\/jats:italic>\n                        parasites, and play a unique immunoregulatory role during infection.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.02825-25","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T13:00:41Z","timestamp":1773147641000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Guanylate-binding proteins balance iNOS\/Arg-1 in myeloid cells during\n                    <i>L. major<\/i>\n                    infection and promote host defense to infection"],"prefix":"10.1128","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7270-5315","authenticated-orcid":false,"given":"Lucy","family":"Fry","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00xcryt71","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, College of Medicine, University of Arkansas for Medical Sciences","place":["Little Rock, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4385-1318","authenticated-orcid":true,"given":"Het","family":"Adhvaryu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00xcryt71","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, College of Medicine, University of Arkansas for Medical Sciences","place":["Little Rock, 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