ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Wilson ME, Jeronimo SM, Pearson RD, 2005. Immunopathogenesis of infection with the visceralizing Leishmania species. Microb Pathog 38: 147–160.
-
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.
-
3.
Klein SL, Flanagan KL, 2016. Sex differences in immune responses. Nat Rev Immunol 16: 626–638.
-
4.
Markle JG, Fish EN, 2014. SeXX matters in immunity. Trends Immunol 35: 97–104.
-
5.
vom Steeg LG, Klein SL, 2016. SeXX matters in infectious disease pathogenesis. PLoS Pathog 12: e1005374.
-
6.
Jansen R et al. 2014. Sex differences in the human peripheral blood transcriptome. BMC Genomics 15: 33.
-
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.
-
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.
-
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: e250–e255.
-
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.
-
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.
-
12.
Lima ID et al. 2012. Leishmania infantum chagasi in northeastern Brazil: asymptomatic infection at the urban perimeter. Am J Trop Med Hyg 86: 99–107.
-
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: 443–449.
-
14.
Guerra-Silveira F, Abad-Franch F, 2013. Sex bias in infectious disease epidemiology: patterns and processes. PLoS One 8: e62390.
-
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: 108–117.
-
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: 3892–3904.
-
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.
-
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: 2288–2296.
-
19.
Snider H, Lezama-Davila C, Alexander J, Satoskar AR, 2009. Sex hormones and modulation of immunity against leishmaniasis. Neuroimmunomodulation 16: 106–113.
-
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: 41–48.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 372 | 327 | 25 |
| Full Text Views | 705 | 9 | 1 |
| PDF Downloads | 174 | 8 | 1 |
Epidemiological and Experimental Evidence for Sex-Dependent Differences in the Outcome of Leishmania infantum Infection
Nilda E. Rodríguez
Nilda E. Rodríguez
Department of Biology, University of Northern Iowa, Cedar Falls, Iowa;
Search for other papers by Nilda E. Rodríguez in
Current site
Google Scholar
PubMed
Search for other papers by Nilda E. Rodríguez in
Current site
Google Scholar
PubMed
Iraci D. Lima
Iraci D. Lima
Fundação Nacional de Saúde, Secretaria de Saúde do Estado do Rio Grande do Norte, Natal, Brazil;
Health Science Post-Graduate Program, Health Science Center, Federal University of Rio Grande do Norte, Natal, Brazil;
Search for other papers by Iraci D. Lima in
Current site
Google Scholar
PubMed
Health Science Post-Graduate Program, Health Science Center, Federal University of Rio Grande do Norte, Natal, Brazil;
Search for other papers by Iraci D. Lima in
Current site
Google Scholar
PubMed
Upasna Gaur Dixit
Upasna Gaur Dixit
Department of Internal Medicine, University of Iowa, Iowa City, Iowa;
Search for other papers by Upasna Gaur Dixit in
Current site
Google Scholar
PubMed
Search for other papers by Upasna Gaur Dixit in
Current site
Google Scholar
PubMed
Elizabeth A. Turcotte
Elizabeth A. Turcotte
Department of Biology, University of Northern Iowa, Cedar Falls, Iowa;
Search for other papers by Elizabeth A. Turcotte in
Current site
Google Scholar
PubMed
Search for other papers by Elizabeth A. Turcotte in
Current site
Google Scholar
PubMed
Ryan D. Lockard
Ryan D. Lockard
Department of Biology, University of Northern Iowa, Cedar Falls, Iowa;
Search for other papers by Ryan D. Lockard in
Current site
Google Scholar
PubMed
Search for other papers by Ryan D. Lockard in
Current site
Google Scholar
PubMed
Hemali Batra-Sharma
Hemali Batra-Sharma
Carver College of Medicine, University of Iowa, Iowa City, Iowa;
Search for other papers by Hemali Batra-Sharma in
Current site
Google Scholar
PubMed
Search for other papers by Hemali Batra-Sharma in
Current site
Google Scholar
PubMed
Eliana L. Nascimento
Eliana L. Nascimento
Health Science Post-Graduate Program, Health Science Center, Federal University of Rio Grande do Norte, Natal, Brazil;
Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, Brazil;
Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, Brazil;
Search for other papers by Eliana L. Nascimento in
Current site
Google Scholar
PubMed
Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, Brazil;
Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, Brazil;
Search for other papers by Eliana L. Nascimento in
Current site
Google Scholar
PubMed
Selma M. B. Jeronimo
Selma M. B. Jeronimo
Health Science Post-Graduate Program, Health Science Center, Federal University of Rio Grande do Norte, Natal, Brazil;
Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, Brazil;
Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, Brazil;
National Institute of Science and Technology of Tropical Diseases, Salvador, Brazil;
Search for other papers by Selma M. B. Jeronimo in
Current site
Google Scholar
PubMed
Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, Brazil;
Institute of Tropical Medicine of Rio Grande do Norte, Federal University of Rio Grande do Norte, Natal, Brazil;
National Institute of Science and Technology of Tropical Diseases, Salvador, Brazil;
Search for other papers by Selma M. B. Jeronimo in
Current site
Google Scholar
PubMed
Mary E. Wilson
Mary E. Wilson
Department of Internal Medicine, University of Iowa, Iowa City, Iowa;
Department of Microbiology, University of Iowa, Iowa City, Iowa;
Veterans’ Affairs Medical Center, Iowa City, Iowa
Search for other papers by Mary E. Wilson in
Current site
Google Scholar
PubMed
Department of Microbiology, University of Iowa, Iowa City, Iowa;
Veterans’ Affairs Medical Center, Iowa City, Iowa
Search for other papers by Mary E. Wilson in
Current site
Google Scholar
PubMed
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
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.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Wilson ME, Jeronimo SM, Pearson RD, 2005. Immunopathogenesis of infection with the visceralizing Leishmania species. Microb Pathog 38: 147–160.
-
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.
-
3.
Klein SL, Flanagan KL, 2016. Sex differences in immune responses. Nat Rev Immunol 16: 626–638.
-
4.
Markle JG, Fish EN, 2014. SeXX matters in immunity. Trends Immunol 35: 97–104.
-
5.
vom Steeg LG, Klein SL, 2016. SeXX matters in infectious disease pathogenesis. PLoS Pathog 12: e1005374.
-
6.
Jansen R et al. 2014. Sex differences in the human peripheral blood transcriptome. BMC Genomics 15: 33.
-
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.
-
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.
-
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: e250–e255.
-
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.
-
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.
-
12.
Lima ID et al. 2012. Leishmania infantum chagasi in northeastern Brazil: asymptomatic infection at the urban perimeter. Am J Trop Med Hyg 86: 99–107.
-
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: 443–449.
-
14.
Guerra-Silveira F, Abad-Franch F, 2013. Sex bias in infectious disease epidemiology: patterns and processes. PLoS One 8: e62390.
-
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: 108–117.
-
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: 3892–3904.
-
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.
-
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: 2288–2296.
-
19.
Snider H, Lezama-Davila C, Alexander J, Satoskar AR, 2009. Sex hormones and modulation of immunity against leishmaniasis. Neuroimmunomodulation 16: 106–113.
-
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: 41–48.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 372 | 327 | 25 |
| Full Text Views | 705 | 9 | 1 |
| PDF Downloads | 174 | 8 | 1 |