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Sex hormones modulate the immune response to Plasmodium berghei ANKA in CBA/Ca mice

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Abstract

Susceptibility to malaria differs between females and males, and this sexual dimorphism may have important implications for the effects of vaccines and drugs. However, little is known about the mechanisms mediating these sexual differences. Because the main differences between sexes are dictated by sex hormones, we studied the effect of gonadal steroids on immune responses to malaria in CBA/Ca mice. We decreased sex hormones levels by gonadectomy and evaluated the splenic index and the cells involved in the immune response, including T cells (CD3+, CD4+, CD8+ and NK+), B cells and macrophages (Mac-3+) in the spleens of female and male mice infected with Plasmodium berghei ANKA. In addition, we measured antibody and cytokine levels in blood. Gonadectomy increased T+ and B+ splenic cells in both sexes but increased Mac-3+ cells only in male mice. By contrast, gonadectomy decreased the NK+ cell population only in male mice. In general, female mice developed higher antibody levels than males. Contrary to our expectations, gonadectomy increased the synthesis of IgG1, IgG2b, IgG3, and total IgG in female mice, indicating negative regulation of antibody production by female sex hormones. Gonadectomy increased the synthesis of tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) only in female mice, suggesting that female sex hormones have anti-inflammatory properties. This work demonstrates that the levels of sex hormones affect the immune response and should be considered when designing malaria vaccines.

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Acknowledgments

We thank Dr. Isaias Salgado-Ugarte for his assistance with the statistical work and Adriana Altamirano Bautista, Román Hernández Meza, Dolores Elizabeth Guzmán Andrade and Everardo González-Acevedo for their assistance with the gonadectomy surgeries. This work was supported by grants from UNAM, PAPIIT grants IN217412 and IN216914.

Conflict of interest

The authors have declared that no conflict of interest exists.

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Authors and Affiliations

  1. Laboratorio de Inmunología Molecular, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Batalla 5 de mayo esq. Fuerte de Loreto, Iztapalapa, 09230, Mexico, DF, Mexico

    Martha Legorreta-Herrera, Néstor Aarón Mosqueda-Romo, Ana Laura Morales-Rodríguez & Fidel Orlando Buendía-González

  2. Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, 62100, Morelos, Mexico

    Karen Elizabeth Nava-Castro

  3. Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Circuito Escolar S/N Ciudad Universitaria, 04510, Mexico, DF, Mexico

    Jorge Morales-Montor

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  1. Martha Legorreta-Herrera
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  2. Néstor Aarón Mosqueda-Romo
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  3. Karen Elizabeth Nava-Castro
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  5. Fidel Orlando Buendía-González
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Correspondence to Martha Legorreta-Herrera.

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Legorreta-Herrera, M., Mosqueda-Romo, N.A., Nava-Castro, K.E. et al. Sex hormones modulate the immune response to Plasmodium berghei ANKA in CBA/Ca mice. Parasitol Res 114, 2659–2669 (2015). https://doi.org/10.1007/s00436-015-4471-6

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  • DOI: https://doi.org/10.1007/s00436-015-4471-6

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