1921
Volume 98, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

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 than females and that mice are a valid model to study this sex-dependent difference.

Loading

Article metrics loading...

The graphs shown below represent data from March 2017
/content/journals/10.4269/ajtmh.17-0563
2017-11-20
2020-09-26
Loading full text...

Full text loading...

/deliver/fulltext/14761645/98/1/tpmd170563.html?itemId=/content/journals/10.4269/ajtmh.17-0563&mimeType=html&fmt=ahah

References

  1. Wilson ME, Jeronimo SM, Pearson RD, 2005. Immunopathogenesis of infection with the visceralizing Leishmania species. Microb Pathog 38: 147160.
    [Google Scholar]
  2. de Freitas EO, Leoratti FM, Freire-de-Lima CG, Morrot A, Feijo DF, 2016. The contribution of immune evasive mechanisms to parasite persistence in visceral leishmaniasis. Front Immunol 7: 153.
    [Google Scholar]
  3. Klein SL, Flanagan KL, 2016. Sex differences in immune responses. Nat Rev Immunol 16: 626638.
    [Google Scholar]
  4. Markle JG, Fish EN, 2014. SeXX matters in immunity. Trends Immunol 35: 97104.
    [Google Scholar]
  5. vom Steeg LG, Klein SL, 2016. SeXX matters in infectious disease pathogenesis. PLoS Pathog 12: e1005374.
    [Google Scholar]
  6. Jansen R et al., 2014. Sex differences in the human peripheral blood transcriptome. BMC Genomics 15: 33.
    [Google Scholar]
  7. Mayne BT, Bianco-Miotto T, Buckberry S, Breen J, Clifton V, Shoubridge C, Roberts CT, 2016. Large scale gene expression meta-analysis reveals tissue-specific, sex-biased gene expression in humans. Front Genet 7: 183.
    [Google Scholar]
  8. Das VN, Pandey RN, Siddiqui NA, Chapman LA, Kumar V, Pandey K, Matlashewski G, Das P, 2016. Longitudinal study of transmission in households with visceral leishmaniasis, asymptomatic infections and PKDL in highly endemic villages in Bihar, India. PLoS Negl Trop Dis 10: e0005196.
    [Google Scholar]
  9. Mukhopadhyay D, Mukherjee S, Ghosh S, Roy S, Saha B, Das NK, Chatterjee M, 2016. A male preponderance in patients with Indian post kala-azar dermal leishmaniasis is associated with increased circulating levels of testosterone. Int J Dermatol 55: e250e255.
    [Google Scholar]
  10. Belo VS, Werneck GL, Barbosa DS, Simoes TC, Nascimento BW, da Silva ES, Struchiner CJ, 2013. Factors associated with visceral leishmaniasis in the Americas: a systematic review and meta-analysis. PLoS Negl Trop Dis 7: e2182.
    [Google Scholar]
  11. Das A, Karthick M, Dwivedi S, Banerjee I, Mahapatra T, Srikantiah S, Chaudhuri I, 2016. Epidemiologic correlates of mortality among symptomatic visceral leishmaniasis cases: findings from situation assessment in high endemic foci in India. PLoS Negl Trop Dis 10: e0005150.
    [Google Scholar]
  12. Lima ID et al., 2012. Leishmania infantum chagasi in northeastern Brazil: asymptomatic infection at the urban perimeter. Am J Trop Med Hyg 86: 99107.
    [Google Scholar]
  13. Jeronimo SM et al., 2004. An emerging peri-urban pattern of infection with Leishmania chagasi, the protozoan causing visceral leishmaniasis in northeast Brazil. Scand J Infect Dis 36: 443449.
    [Google Scholar]
  14. Guerra-Silveira F, Abad-Franch F, 2013. Sex bias in infectious disease epidemiology: patterns and processes. PLoS One 8: e62390.
    [Google Scholar]
  15. Thalhofer CJ, Chen Y, Sudan B, Love-Homan L, Wilson ME, 2011. Leukocytes infiltrate the skin and draining lymph nodes in response to the protozoan Leishmania infantum chagasi. Infect Immun 79: 108117.
    [Google Scholar]
  16. Weirather JL et al., 2011. Serial quantitative PCR assay for detection, species discrimination, and quantification of Leishmania spp. in human samples. J Clin Microbiol 49: 38923904.
    [Google Scholar]
  17. Rodriguez NE, Gaur Dixit U, Allen LA, Wilson ME, 2011. Stage-specific pathways of Leishmania infantum chagasi entry and phagosome maturation in macrophages. PLoS One 6: e19000.
    [Google Scholar]
  18. Travi BL, Osorio Y, Melby PC, Chandrasekar B, Arteaga L, Saravia NG, 2002. Gender is a major determinant of the clinical evolution and immune response in hamsters infected with Leishmania spp. Infect Immun 70: 22882296.
    [Google Scholar]
  19. Snider H, Lezama-Davila C, Alexander J, Satoskar AR, 2009. Sex hormones and modulation of immunity against leishmaniasis. Neuroimmunomodulation 16: 106113.
    [Google Scholar]
  20. Weirather JL, Duggal P, Nascimento EL, Monteiro GR, Martins DR, Lacerda HG, Fakiola M, Blackwell JM, Jeronimo SM, Wilson ME, 2017. Comprehensive candidate gene analysis for symptomatic or asymptomatic outcomes of Leishmania infantum infection in Brazil. Ann Hum Genet 81: 4148.
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.17-0563
Loading
/content/journals/10.4269/ajtmh.17-0563
Loading

Data & Media loading...

  • Received : 14 Jul 2017
  • Accepted : 25 Sep 2017
  • Published online : 20 Nov 2017
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error