Testosterone induces sexual dimorphism during infection with Plasmodium berghei ANKA
Malaria is the most lethal parasitic disease worldwide; men exhibit higher mortality and more severe symptomatology than women; however, in most studies of immune response in malaria, sex is not considered a variable. Sex hormones 17β-oestradiol and testosterone are responsible for the main physiolo...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.968325/full |
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| author | Jesús Aguilar-Castro Jesús Aguilar-Castro Luis Antonio Cervantes-Candelas Luis Antonio Cervantes-Candelas Fidel Orlando Buendía-González Fidel Orlando Buendía-González Omar Fernández-Rivera Omar Fernández-Rivera Teresita de Jesús Nolasco-Pérez Teresita de Jesús Nolasco-Pérez Monserrat Sofía López-Padilla David Roberto Chavira-Ramírez Armando Cervantes-Sandoval Martha Legorreta-Herrera |
| author_facet | Jesús Aguilar-Castro Jesús Aguilar-Castro Luis Antonio Cervantes-Candelas Luis Antonio Cervantes-Candelas Fidel Orlando Buendía-González Fidel Orlando Buendía-González Omar Fernández-Rivera Omar Fernández-Rivera Teresita de Jesús Nolasco-Pérez Teresita de Jesús Nolasco-Pérez Monserrat Sofía López-Padilla David Roberto Chavira-Ramírez Armando Cervantes-Sandoval Martha Legorreta-Herrera |
| author_sort | Jesús Aguilar-Castro |
| collection | DOAJ |
| description | Malaria is the most lethal parasitic disease worldwide; men exhibit higher mortality and more severe symptomatology than women; however, in most studies of immune response in malaria, sex is not considered a variable. Sex hormones 17β-oestradiol and testosterone are responsible for the main physiological differences between sexes. When interacting with their receptors on different immune cells, they modify the expression of genes that modulate cell proliferation, differentiation, and synthesis of cytokines. The immunosuppressive activity of testosterone is well accepted; however, its participation in the sexual dimorphism of the immune response to malaria has not been studied. In this work, we analysed whether altering the concentration of testosterone, through increasing the concentration of this hormone for exogenous administration for three weeks, or gonadectomy before infection with Plasmodium berghei ANKA affects different cells of the immune response necessary for parasite clearance. We also assessed the concentration of pro-and anti-inflammatory cytokines in male and female CBA/Ca mice infected or not with the parasite. Our results show that testosterone changes affect females more than males, resulting in sex-associated patterns. Testosterone administration increased parasitaemia in intact males while reducing it in intact females leading to a dimorphic pattern. In addition, gonadectomy increased parasitaemia in both sexes. Moreover, testosterone administration prevented both weight loss caused by the infection in females and hypothermia in gonadectomized mice of both sexes. Boosting testosterone concentration increased CD3+ and CD8+ populations but decreased the B220+ cells exclusively in females. Additionally, testosterone reduced IFN-γ concentration and increased IL-6 levels only in females, while in males, testosterone increased the number of NK cells. Finally, gonadectomy decreased TNF-α concentration in both sexes. Our results demonstrate that testosterone induces different patterns depending on sex and testosterone concentration. The results of this work contribute to understanding the impact of modifying testosterone concentration on the immune response specific against Plasmodium and the participation of this hormone in sexual dimorphism in malaria. |
| first_indexed | 2024-04-12T18:13:27Z |
| format | Article |
| id | doaj.art-db904334676e4eff8e63573fe081fd3a |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-12T18:13:27Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-db904334676e4eff8e63573fe081fd3a2022-12-22T03:21:44ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-09-011210.3389/fcimb.2022.968325968325Testosterone induces sexual dimorphism during infection with Plasmodium berghei ANKAJesús Aguilar-Castro0Jesús Aguilar-Castro1Luis Antonio Cervantes-Candelas2Luis Antonio Cervantes-Candelas3Fidel Orlando Buendía-González4Fidel Orlando Buendía-González5Omar Fernández-Rivera6Omar Fernández-Rivera7Teresita de Jesús Nolasco-Pérez8Teresita de Jesús Nolasco-Pérez9Monserrat Sofía López-Padilla10David Roberto Chavira-Ramírez11Armando Cervantes-Sandoval12Martha Legorreta-Herrera13Unidad de Investigación Química Computacional, Síntesis y Farmacología de Moléculas de Interés Biológico. Laboratorio de Inmunología Molecular, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, MexicoPosgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Ciudad de México, MexicoUnidad de Investigación Química Computacional, Síntesis y Farmacología de Moléculas de Interés Biológico. Laboratorio de Inmunología Molecular, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, MexicoPosgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Ciudad de México, MexicoUnidad de Investigación Química Computacional, Síntesis y Farmacología de Moléculas de Interés Biológico. Laboratorio de Inmunología Molecular, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, MexicoPosgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Ciudad de México, MexicoUnidad de Investigación Química Computacional, Síntesis y Farmacología de Moléculas de Interés Biológico. Laboratorio de Inmunología Molecular, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, MexicoPosgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Ciudad de México, MexicoUnidad de Investigación Química Computacional, Síntesis y Farmacología de Moléculas de Interés Biológico. Laboratorio de Inmunología Molecular, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, MexicoPosgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Ciudad de México, MexicoUnidad de Investigación Química Computacional, Síntesis y Farmacología de Moléculas de Interés Biológico. Laboratorio de Inmunología Molecular, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, MexicoDepartamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, MexicoLaboratorio de Aplicaciones Computacionales, Facultad de Estudios Superiores Zaragoza, UNAM, Ciudad de México, MexicoUnidad de Investigación Química Computacional, Síntesis y Farmacología de Moléculas de Interés Biológico. Laboratorio de Inmunología Molecular, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, MexicoMalaria is the most lethal parasitic disease worldwide; men exhibit higher mortality and more severe symptomatology than women; however, in most studies of immune response in malaria, sex is not considered a variable. Sex hormones 17β-oestradiol and testosterone are responsible for the main physiological differences between sexes. When interacting with their receptors on different immune cells, they modify the expression of genes that modulate cell proliferation, differentiation, and synthesis of cytokines. The immunosuppressive activity of testosterone is well accepted; however, its participation in the sexual dimorphism of the immune response to malaria has not been studied. In this work, we analysed whether altering the concentration of testosterone, through increasing the concentration of this hormone for exogenous administration for three weeks, or gonadectomy before infection with Plasmodium berghei ANKA affects different cells of the immune response necessary for parasite clearance. We also assessed the concentration of pro-and anti-inflammatory cytokines in male and female CBA/Ca mice infected or not with the parasite. Our results show that testosterone changes affect females more than males, resulting in sex-associated patterns. Testosterone administration increased parasitaemia in intact males while reducing it in intact females leading to a dimorphic pattern. In addition, gonadectomy increased parasitaemia in both sexes. Moreover, testosterone administration prevented both weight loss caused by the infection in females and hypothermia in gonadectomized mice of both sexes. Boosting testosterone concentration increased CD3+ and CD8+ populations but decreased the B220+ cells exclusively in females. Additionally, testosterone reduced IFN-γ concentration and increased IL-6 levels only in females, while in males, testosterone increased the number of NK cells. Finally, gonadectomy decreased TNF-α concentration in both sexes. Our results demonstrate that testosterone induces different patterns depending on sex and testosterone concentration. The results of this work contribute to understanding the impact of modifying testosterone concentration on the immune response specific against Plasmodium and the participation of this hormone in sexual dimorphism in malaria.https://www.frontiersin.org/articles/10.3389/fcimb.2022.968325/fullmalariaimmune responsesexual dimorphismtestosteronePlasmodium berghei ANKA |
| spellingShingle | Jesús Aguilar-Castro Jesús Aguilar-Castro Luis Antonio Cervantes-Candelas Luis Antonio Cervantes-Candelas Fidel Orlando Buendía-González Fidel Orlando Buendía-González Omar Fernández-Rivera Omar Fernández-Rivera Teresita de Jesús Nolasco-Pérez Teresita de Jesús Nolasco-Pérez Monserrat Sofía López-Padilla David Roberto Chavira-Ramírez Armando Cervantes-Sandoval Martha Legorreta-Herrera Testosterone induces sexual dimorphism during infection with Plasmodium berghei ANKA Frontiers in Cellular and Infection Microbiology malaria immune response sexual dimorphism testosterone Plasmodium berghei ANKA |
| title | Testosterone induces sexual dimorphism during infection with Plasmodium berghei ANKA |
| title_full | Testosterone induces sexual dimorphism during infection with Plasmodium berghei ANKA |
| title_fullStr | Testosterone induces sexual dimorphism during infection with Plasmodium berghei ANKA |
| title_full_unstemmed | Testosterone induces sexual dimorphism during infection with Plasmodium berghei ANKA |
| title_short | Testosterone induces sexual dimorphism during infection with Plasmodium berghei ANKA |
| title_sort | testosterone induces sexual dimorphism during infection with plasmodium berghei anka |
| topic | malaria immune response sexual dimorphism testosterone Plasmodium berghei ANKA |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.968325/full |
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