{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T05:51:54Z","timestamp":1784872314881,"version":"3.55.0"},"posted":{"date-parts":[[2026,6,12]]},"group-title":"Immunology","reference-count":47,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R37AI167750"],"award-info":[{"award-number":["R37AI167750"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P30AI16843"],"award-info":[{"award-number":["P30AI16843"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Tuberculosis (TB), the world\u2019s deadliest infection, shows higher prevalence and mortality in males than females (M\/F ratio &gt;1.7). Using Four Core Genotype (FCG) mice to decouple gonadal from chromosomal sex (XX, XY gonadal males and XX, XY gonadal females), we show that gonadal males develop accelerated disease driven by dysfunctional myeloid responses rather than impaired bacterial recognition. Both XX and XY males exhibited increased mortality, higher Mycobacterium tuberculosis (Mtb) burden, and severe lung pathology. Mechanistically, gonadal male susceptibility involved early myeloid priming, excessive neutrophil recruitment, CCR2\u207a monocyte accumulation, and hyperinflammation, with enhanced neutrophil extracellular trap (NET) formation and disorganized granulomas, implicating testes and androgens as key drivers of male susceptibility. While XY gonadal females were less susceptible, XX gonadal females showed the greatest resistance, associated with coordinated T\u2013 and B-cell responses and enhanced B-cell follicle formation. Together, these findings identify gonad-driven myeloid dysregulation as a central mechanism underlying male TB susceptibility.<\/jats:p>","DOI":"10.64898\/2026.06.11.731661","type":"posted-content","created":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T01:20:23Z","timestamp":1781313623000},"source":"Crossref","is-referenced-by-count":2,"title":["Gonadal regulation of sex-specific immunity in tuberculosis: enhanced lymphocyte function in females and dysfunctional myeloid responses in males"],"prefix":"10.64898","author":[{"given":"Manish","family":"Gupta","sequence":"first","affiliation":[{"name":"Center for TB Research, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21287"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishtha","family":"Nayyar","sequence":"additional","affiliation":[{"name":"ICAR-NBAIR, Bengaluru, 560024, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Shen","sequence":"additional","affiliation":[{"name":"Center for TB Research, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21287"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shichun","family":"Lun","sequence":"additional","affiliation":[{"name":"Center for TB Research, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD 21287"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabal","family":"Chaulagain","sequence":"additional","affiliation":[{"name":"W. 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