{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:56:19Z","timestamp":1790657779366,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DGAPA","award":["IN228620"],"award-info":[{"award-number":["IN228620"]}]},{"name":"DGAPA","award":["IN223524"],"award-info":[{"award-number":["IN223524"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Malaria exhibits pronounced sexual dimorphism, with males experiencing greater disease severity and mortality than females do. Although these differences have been partially attributed to the immunosuppressive effects of testosterone, the underlying mechanisms remain poorly understood. Here, we investigated the role of testosterone in sex-specific immune responses by administering a combination of letrozole and testosterone (LT) to male and female mice infected with Plasmodium berghei ANKA. LT treatment increased testosterone concentrations in both sexes and was associated with higher parasitemia, and splenic index mainly in males, whereas hemoglobin levels decreased only in males. In females, LT increased macrophage numbers, reduced B-cell numbers, enhanced IgM production, increased androgen receptor (AR) expression, and decreased estrogen receptor-\u03b1 (ER\u03b1) expression. In contrast, LT selectively reduced IL-17A levels in males without modifying AR expression. In addition, the IL-2, IFN-\u03b3, and IL-10 levels remained unchanged in both sexes. These findings demonstrate that testosterone differentially regulates immune responses during malaria through sex-specific modulation of steroid hormone receptor expression. This study provides insight into how testosterone contributes to sex-dependent immune responses to malaria. In turn, elucidating the role of testosterone in these differences may help identify new therapeutic opportunities tailored to biological sex and ultimately contribute to the development of more effective strategies for managing infectious diseases.<\/jats:p>","DOI":"10.3390\/ijms27198649","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:50:54Z","timestamp":1790614254000},"page":"8649","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Testosterone Regulates Sex-Dependent Immune Responses and Androgen Receptor Expression During Plasmodium berghei ANKA Infection"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8134-833X","authenticated-orcid":false,"given":"Teresita de Jes\u00fas","family":"Nolasco-P\u00e9rez","sequence":"first","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Molecular, Unidad de Investigaci\u00f3n Qu\u00edmica Computacional, S\u00edntesis y Farmacolog\u00eda de Mol\u00e9culas de Inter\u00e9s Biol\u00f3gico, Divisi\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Iztapalapa, Ciudad de M\u00e9xico 09230, Mexico"},{"name":"Posgrado en Ciencias Biol\u00f3gicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Unidad de Posgrado, Edificio D, 1\u00b0 Piso, Circuito de Posgrados, Ciudad Universitaria, Coyoac\u00e1n, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Luis Antonio","family":"Cervantes-Candelas","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Molecular, Unidad de Investigaci\u00f3n Qu\u00edmica Computacional, S\u00edntesis y Farmacolog\u00eda de Mol\u00e9culas de Inter\u00e9s Biol\u00f3gico, Divisi\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Iztapalapa, Ciudad de M\u00e9xico 09230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"software","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3620-7858","authenticated-orcid":false,"given":"V\u00edctor Hugo","family":"Salazar-Casta\u00f1\u00f3n","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Molecular, Unidad de Investigaci\u00f3n Qu\u00edmica Computacional, S\u00edntesis y Farmacolog\u00eda de Mol\u00e9culas de Inter\u00e9s Biol\u00f3gico, Divisi\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Iztapalapa, Ciudad de M\u00e9xico 09230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Fidel Orlando","family":"Buend\u00eda-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Molecular, Unidad de Investigaci\u00f3n Qu\u00edmica Computacional, S\u00edntesis y Farmacolog\u00eda de Mol\u00e9culas de Inter\u00e9s Biol\u00f3gico, Divisi\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Iztapalapa, Ciudad de M\u00e9xico 09230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"David Roberto","family":"Chavira-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda de la Reproducci\u00f3n, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Ciudad de M\u00e9xico 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5985-7365","authenticated-orcid":false,"given":"Martha","family":"Legorreta-Herrera","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda Molecular, Unidad de Investigaci\u00f3n Qu\u00edmica Computacional, S\u00edntesis y Farmacolog\u00eda de Mol\u00e9culas de Inter\u00e9s Biol\u00f3gico, Divisi\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Iztapalapa, Ciudad de M\u00e9xico 09230, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025). 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