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Epidemiological and Experimental Evidence for Sex-Dependent Differences in the Outcome of Leishmania infantum Infection

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  • 1 Department of Biology, University of Northern Iowa, Cedar Falls, Iowa;
  • | 2 Fundação Nacional de Saúde, Secretaria de Saúde do Estado do Rio Grande do Norte, Natal, Brazil;
  • | 3 Health Science Post-Graduate Program, Health Science Center, Federal University of Rio Grande do Norte, Natal, Brazil;
  • | 4 Department of Internal Medicine, University of Iowa, Iowa City, Iowa;
  • | 5 Carver College of Medicine, University of Iowa, Iowa City, Iowa;
  • | 6 Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, Brazil;
  • | 7 Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, Brazil;
  • | 8 National Institute of Science and Technology of Tropical Diseases, Salvador, Brazil;
  • | 9 Department of Microbiology, University of Iowa, Iowa City, Iowa;
  • | 10 Veterans’ Affairs Medical Center, Iowa City, Iowa

Leishmania infantum causes visceral leishmaniasis (VL) in Brazil. We previously observed that VL is more common in males than females living in endemic neighborhoods, despite similar exposure. Using a larger sample, we document that VL is more common in males than females, but only after puberty. BALB/c and C57BL/6 mouse models confirmed that there is a biological basis for male susceptibility to symptomatic VL, showing higher parasite burdens in males than females. Female C57BL/6 mice generated more antigen-induced cytokines associated with curative responses (interferon-γ, interleukin [IL]-1β). Males expressed higher levels of IL-10 and tumor necrosis factor, which are linked to exacerbated disease. Different parasite lines entered or survived at a higher rate in macrophages of male- than female-origin. These results suggest that males are inherently more susceptible to L. infantum than females and that mice are a valid model to study this sex-dependent difference.

Author Notes

Address correspondence to Nilda E. Rodríguez, Department of Biology, University of Northern Iowa, 85 McCollum Science Hall, Cedar Falls, IA 50614-0421. E-mail: nilda.rodriguez@uni.edu

Financial support: This work was supported in part by funds from the University of Northern Iowa Graduate College (N. E. R., R. D. L.), the College of Humanities, Arts and Sciences (N. E. R., E. A. T.), and the Dr. Robert and Brenda Good Undergraduate Research Assistantship (E.A.T.). Additional support was provided by a Career Developmental Award from the Department of Veterans Affairs (N. E. R.), VA grants 5I01BX001983 and 2I01BX000536 (M. E. W.) and NIH grants R01 AI076233 (M. E. W.) and NIH Tropical Medicine Research Center P50 AI-30639 (M. E. W. and S. M. B. J.), and National Institute of Science and Technology of Tropical Diseases.

Authors’ addresses: Nilda E. Rodríguez, Elizabeth A. Turcotte, and Ryan D. Lockard, Department of Biology, University of Northern Iowa, Cedar Falls, IA, E-mails: nilda.rodriguez@uni.edu, turcotte@uni.edu, and lockardr@uni.edu. Iraci D. Lima, Fundação Nacional de Saúde, Secretaria de Saúde do Estado do Rio Grande do Norte, Natal, Brazil, E-mail: iraciduarte.lima@gmail.com. Upasna Gaur Dixit, Department of Internal Medicine, University of Iowa, Iowa City, IA, E-mail: upasnadixit5@gmail.com. Hemali Batra-Sharma, Carver College of Medicine, University of Iowa, Iowa City, IA, E-mail: hemalibatra@gmail.com. Eliana L. Nascimento, Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, Brazil, and the Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, Brazil, E-mail: eltomaz@gmail.com. Selma M. B. Jeronimo, Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, Brazil, and the Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, Brazil, and the National Institute of Science and Technology of Tropical Diseases, Salvador, Brazil, E-mail: selma.b.jeronimo@gmail.com. Mary E. Wilson, Departments of Internal Medicine and Microbiology, University of Iowa, Iowa City, IA, and Veterans’ Affairs Medical Center, Iowa City, IA, E-mail: mary-wilson@uiowa.edu.

These authors contributed equally to this work.

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