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Diet-induced obesity promotes systemic inflammation and increased susceptibility to murine visceral leishmaniasis

Published online by Cambridge University Press:  21 July 2016

GLÊNIA DAROS SARNÁGLIA ,
LUCIANA POLACO COVRE ,
FAUSTO EDMUNDO LIMA PEREIRA ,
HERBERT LEONEL DE MATOS GUEDES ,
ANA MARIA CAETANO FARIA ,
REYNALDO DIETZE ,
RODRIGO RIBEIRO RODRIGUES ,
TATIANI UCELI MAIOLI  and
DANIEL CLÁUDIO OLIVIERA GOMES
GLÊNIA DAROS SARNÁGLIA
Affiliation:
Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo – UFES, Vitória, Brazil
LUCIANA POLACO COVRE
Affiliation:
Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo – UFES, Vitória, Brazil
FAUSTO EDMUNDO LIMA PEREIRA
Affiliation:
Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo – UFES, Vitória, Brazil
HERBERT LEONEL DE MATOS GUEDES
Affiliation:
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
ANA MARIA CAETANO FARIA
Affiliation:
Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
REYNALDO DIETZE
Affiliation:
Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo – UFES, Vitória, Brazil
RODRIGO RIBEIRO RODRIGUES
Affiliation:
Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo – UFES, Vitória, Brazil
TATIANI UCELI MAIOLI
Affiliation:
Departamento de Nutrição, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
DANIEL CLÁUDIO OLIVIERA GOMES*
Affiliation:
Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo – UFES, Vitória, Brazil Núcleo de Biotecnologia, Universidade Federal do Espírito Santo – UFES, Vitória, Brazil
*
*Corresponding author. Laboratório de Imunobiologia, Núcleo de Doenças Infecciosas/Núcleo de Biotecnologia, Universidade Federal do Espirito Santo – UFES, Av. Marechal Campos, 1468 – Maruípe, Vitória – ES, Cep 29040-091, Brazil. E-mail: dgomes@ndi.ufes.br
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Summary

Obesity is the main causal factor for metabolic syndrome and chronic systemic inflammation, which impacts on immune function and increases susceptibility to pathogens. Here, we investigated the effect of obesity on the outcome of visceral leishmaniasis caused by Leishmaniasis infantum chagasi. C57BL/6 mice fed with high-sugar and butter diet (HSB) showed a significant increase in body weight, adiposity index and morphological changes in adipocyte. To investigate the consequences of obesity on the specific immunity against Leishmania, both control and HSB diet groups were infected with 107L. infantum chagasi promastigotes in the eighth-week after diet started and euthanized 4 weeks later. HSB-diet fed mice exhibited a significantly higher parasite burden in both liver and spleen compared with control- diet group. Gonadal adipocyte tissue from HSB-diet mice showed increased TNF-α, IL-6 and leptin and diminished IL-10 production compared with control. Cytokines production analysis in the spleen and liver from these animals also demonstrated higher production of IFN-γ, TNF-α, IL-6 and nitric oxide and diminished production of IL-10 and TGF-β, which correlate with inflammatory foci and the cell hyperplasia observed. Taken together, obesity can interfere with responses to pathogen-derived signals and impair the development of protective anti-Leishmania immunity.

Keywords

Leishmania infantum chagasihigh-sugar and butter dietexperimental obesity
Type
Research Article
Information
Parasitology , Volume 143 , Issue 12 , October 2016 , pp. 1647 - 1655
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Copyright
Copyright © Cambridge University Press 2016 

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References

REFERENCES

Alimohammadian, M. H., Darabi, H., Ajdary, S., Khaze, V. and Torkabadi, E. (2010). Genotypically distinct strains of Leishmania major display diverse clinical and immunological patterns in BALB/c mice. Infection, Genetics and Evolution 10, 969–975.CrossRefGoogle ScholarPubMed
Bacellar, O., Lessa, H., Schriefer, A., Machado, P., De Jesus, A. R., Dutra, W. O., Gollob, K. J. and Carvalho, E. M. (2002). Up-regulation of Th1-type responses in mucosal leishmaniasis patients. Infection and Immunity 70, 6734–6740.CrossRefGoogle ScholarPubMed
Barth, K., Remick, D. G. and Genco, C. A. (2013). Disruption of immune regulation by microbial pathogens and resulting chronic inflammation. Journal of Cellular Physiology 228, 1413–1422.CrossRefGoogle ScholarPubMed
Carvalho, A. M., Amorim, C. F., Barbosa, J. L. S., Lago, A. S. and Carvalho, E. M. (2015). Age modifies the immunologic response and clinical presentation of American tegumentary leishmaniasis. American Journal of Tropical Medicine and Hygiene 92, 1173–1177.CrossRefGoogle ScholarPubMed
Carvalho, L. P., Passos, S., Bacellar, O., Lessa, M., Almeida, R. P., Magalhães, A., Dutra, W. O., Gollob, K. J., Machado, P. and Ribeiro De Jesus, A. (2007). Differential immune regulation of activated T cells between cutaneous and mucosal leishmaniasis as a model for pathogenesis. Parasite Immunology 29, 251–258.CrossRefGoogle Scholar
Castellucci, L., Jamieson, S. E., Almeida, L., Oliveira, J., Guimaraes, L. H., Lessa, M., Fakiola, M., Jesus, A. R., Nancy Miller, E., Carvalho, E. M. and Blackwell, J. M. (2012). Wound healing genes and susceptibility to cutaneous leishmaniasis in Brazil. Infection, Genetics and Evolution 12, 1102–1110.CrossRefGoogle ScholarPubMed
Chen, S., Akbar, S. M. F., Miyake, T., Abe, M., Al-Mahtab, M., Furukawa, S., Bunzo, M., Hiasa, Y. and Onji, M. (2014). Diminished immune response to vaccinations in obesity: role of myeloid-derived suppressor and other myeloid cells. Obesity Research & Clinical Practice 9, 35–44.CrossRefGoogle ScholarPubMed
De Oliveira Gomes, D. C., Da Silva Costa Souza, B. L., De Matos Guedes, H. L., Lopes, U. G. and Rossi-Bergmann, B. (2011). Intranasal immunization with LACK-DNA promotes protective immunity in hamsters challenged with Leishmania chagasi . Parasitology 138, 1892–1897.CrossRefGoogle ScholarPubMed
Easterbrook, J. D., Dunfee, R. L., Schwartzman, L. M., Jagger, B. W., Sandouk, A., Kash, J. C., Memoli, M. J. and Taubenberger, J. K. (2011). Obese mice have increased morbidity and mortality compared to non-obese mice during infection with the 2009 pandemic H1N1 influenza virus. Influenza and Other Respiratory Viruses 5, 418–425.CrossRefGoogle ScholarPubMed
Faria, D. R., Gollob, K. J., Barbosa, J., Schriefer, A., Machado, P. R. L., Lessa, H., Carvalho, L. P., Romano-Silva, M. A., De Jesus, A. R., Carvalho, E. M. and Dutra, W. O. (2005). Decreased in situ expression of interleukin-10 receptor is correlated with the exacerbated inflammatory and cytotoxic responses observed in mucosal leishmaniasis. Infection and Immunity 73, 7853–7859.CrossRefGoogle ScholarPubMed
Farmaki, E., Kanakoudi-Tsakalidou, F., Spoulou, V., Trachana, M., Pratsidou-Gertsi, P., Tritsoni, M. and Theodoridou, M. (2010). The effect of anti-TNF treatment on the immunogenicity and safety of the 7-valent conjugate pneumococcal vaccine in children with juvenile idiopathic arthritis. Vaccine 28, 5109–5113.CrossRefGoogle ScholarPubMed
Fuentes, L., Roszer, T. and Ricote, M. (2010). Inflammatory mediators and insulin resistance in obesity: role of nuclear receptor signaling in macrophages. Mediators of Inflammation 2010, 219583.CrossRefGoogle ScholarPubMed
Gaze, S. T., Dutra, W. O., Lessa, M., Lessa, H., Guimarães, L. H., De Jesus, A. R., Carvalho, L. P., Machado, P., Carvalho, E. M. and Gollob, K. J. (2006). Mucosal leishmaniasis patients display an activated inflammatory T-cell phenotype associated with a nonbalanced monocyte population. Scandinavian Journal of Immunology 63, 70–78.CrossRefGoogle ScholarPubMed
Green, L. C., Wagner, D. A., Glogowski, J., Skipper, P. L., Wishnok, J. S. and Tannenbaum, S. R. (1982). Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Analytical Biochemistry 126, 131–138.CrossRefGoogle ScholarPubMed
Gregor, M. F. and Hotamisligil, G. S. (2011). Inflammatory mechanisms in obesity. Annual Review of Immunology 29, 415–445.CrossRefGoogle ScholarPubMed
Hailu, A., Van Der Poll, T., Berhe, N. and Kager, P. A. (2004). Elevated plasma levels of interferon (IFN)-gamma, IFN-gamma inducing cytokines, and IFN-gamma inducible CXC chemokines in visceral leishmaniasis. American Journal of Tropical Medicine and Hygiene 71, 561–567.Google ScholarPubMed
Jovicic, N., Jeftic, I., Jovanovic, I., Radosavljevic, G., Arsenijevic, N., Lukic, M. L. and Pejnovic, N. (2015). Differential immunometabolic phenotype in Th1 and Th2 dominant mouse strains in response to high-fat feeding. PLoS ONE 10, 1–21.CrossRefGoogle ScholarPubMed
Kaye, P. M., Svensson, M., Ato, M., Maroof, A., Polley, R., Stager, S., Zubairi, S. and Engwerda, C. R. (2004). The immunopathology of experimental visceral leishmaniasis. Immunological Reviews 201, 239–253.CrossRefGoogle ScholarPubMed
Kentish, S. J., Frisby, C. L., Kritas, S., Li, H., Hatzinikolas, G., O'Donnell, T. A., Wittert, G. A. and Page, A. J. (2015). TRPV1 channels and gastric vagal afferent signalling in lean and high fat diet induced obese mice. PloS ONE 10, e0135892.CrossRefGoogle ScholarPubMed
Kraus, S. and Arber, N. (2009). Inflammation and colorectal cancer. Current Opinion in Pharmacology 9, 405–410.CrossRefGoogle ScholarPubMed
Kumar, R., Singh, N., Gautam, S., Singh, O. P., Gidwani, K., Rai, M., Sacks, D., Sundar, S. and Nylen, S. (2014). Leishmania specific CD4T cells release IFN-γ that limits parasite replication in patients with visceral leishmaniasis. PLoS Neglected Tropical Diseases 8, e3198.Google Scholar
Leal, J. M., Mosquini, M., Covre, L. P., Stagmiller, N. P., Rodrigues, R. R., Christensen, D., Guedes, H. L. D. M., Rossi-Bergmann, B. and Gomes, D. C. D. O. (2015). Intranasal vaccination with killed Leishmania amazonensis promastigotes antigen (LaAg) associated with CAF01 adjuvant induces partial protection in BALB/c mice challenged with Leishmania (infantum) chagasi . Parasitology 142, 1640–1646.CrossRefGoogle ScholarPubMed
Liu, L., Li, Q., Xiao, X., Wu, C., Gao, R., Peng, C., Li, D., Zhang, W., Du, T., Wang, Y., Yang, S., Zhen, Q. and Ge, Q. (2016). miR-1934, downregulated in obesity, protects against low-grade inflammation in adipocytes. Molecular and Cellular Endocrinology 428, 109–117.CrossRefGoogle ScholarPubMed
Louie, J. K., Acosta, M., Samuel, M. C., Schechter, R., Vugia, D. J., Harriman, K. and Matyas, B. T. (2011). A novel risk factor for a novel virus: obesity and 2009 pandemic influenza A (H1N1). Clinical Infectious Diseases: an Official Publication of the Infectious Diseases Society of America 52, 301–312.CrossRefGoogle ScholarPubMed
Maioli, T. U., Gonçalves, J. L., Miranda, M. C. G., Martins, V. D., Horta, L. S., Moreira, T. G., Godard, A. L. B., Santiago, A. F. and Faria, A. M. C. (2015). High sugar and butter (HSB) diet induces obesity and metabolic syndrome with decrease in regulatory T cells in adipose tissue of mice. Inflammation Research 65, 169–178.CrossRefGoogle ScholarPubMed
Malafaia, G., Serafim, T. D., Silva, M. E., Pedrosa, M. L. and Rezende, S. A. (2009). Protein-energy malnutrition decreases immune response to Leishmania chagasi vaccine in BALB/c mice. Parasite Immunology 31, 41–49.CrossRefGoogle ScholarPubMed
Marques-Da-Silva, E. A., Coelho, E. A. F., Gomes, D. C. O., Vilela, M. C., Masioli, C. Z., Tavares, C. A. P., Fernandes, A. P., Afonso, L. C. C. and Rezende, S. A. (2005). Intramuscular immunization with p36(LACK) DNA vaccine induces IFN-γ production but does not protect BALB/c mice against Leishmania chagasi intravenous challenge. Parasitology Research 98, 67–74.CrossRefGoogle Scholar
Melby, P. C., Yang, J., Zhao, W., Perez, L. E. and Cheng, J. (2001). Leishmania donovani p36(LACK) DNA vaccine is highly immunogenic but not protective against experimental visceral leishmaniasis. Infection and Immunity 69, 4719–4725.CrossRefGoogle Scholar
Murray, H. W. (2001). Tissue granuloma structure-function in experimental visceral leishmaniasis. International Journal of Experimental Pathology 82, 249–267.CrossRefGoogle ScholarPubMed
Nagajyothi, F., Weiss, L. M., Zhao, D., Koba, W., Jelicks, L. A., Cui, M.-H., Factor, S. M., Scherer, P. E. and Tanowitz, H. B. (2014). High fat diet modulates Trypanosoma cruzi infection associated myocarditis. PLoS Neglected Tropical Diseases 8, e3118.CrossRefGoogle ScholarPubMed
Neves, R. H., Miranda de Barros Alencar, A. C., Costa-Silva, M., Águila, M. B., Mandarim-de-Lacerda, C. A., Machado-Silva, J. R. and Gomes, D. C. (2007). Long-term feeding a high-fat diet causes histological and parasitological effects on murine schistosomiasis mansoni outcome. Experimental Parasitology 115, 324–332.CrossRefGoogle ScholarPubMed
Nylén, S., Maurya, R., Eidsmo, L., Manandhar, KD., Sundar, S. and Sacks, D. (2007). Splenic accumulation of IL-10 mRNA in T cells distinct from CD4+CD25+ (Foxp3) regulatory T cells in human visceral leishmaniasis. Journal of Experimental Medicine 204, 805–817.CrossRefGoogle Scholar
Onofrio, L. I., Arocena, A. R., Paroli, A. F., Cabalén, M. E., Andrada, M. C., Cano, R. C. and Gea, S. (2015). Trypanosoma cruzi infection is a potent risk factor for non-alcoholic steatohepatitis enhancing local and systemic inflammation associated with strong oxidative stress and metabolic disorders. PLoS Neglected Tropical Diseases 9, e0003464.CrossRefGoogle ScholarPubMed
Ouchi, N. and Walsh, K. (2007). Adiponectin as an anti-inflammatory factor. Clinica Chimica Acta; International Journal of Clinical Chemistry 380, 24–30.CrossRefGoogle ScholarPubMed
Ouchi, N., Parker, J. L., Lugus, J. J. and Walsh, K. (2011). Adipokines in inflammation and metabolic disease. Nature Reviews. Immunology 11, 85–97.CrossRefGoogle ScholarPubMed
Pereira-Carvalho, R., Mendes-Aguiar, C. O., Oliveira-Neto, M. P., Covas, C. J. F., Bertho, Á. L., Da-Cruz, A. M. and Gomes-Silva, A. (2013). Leishmania braziliensis-reactive T cells are down-regulated in long-term cured cutaneous leishmaniasis, but the renewal capacity of T effector memory compartments is preserved. PLoS ONE 8, 1–8.CrossRefGoogle ScholarPubMed
Pirmez, C., Yamamura, M., Uyemura, K., Paes-Oliveira, M., Conceicao-Silva, F. and Modlin, R. L. (1993). Cytokine patterns in the pathogenesis of human leishmaniasis. Journal of Clinical Investigation 91, 1390–1395.CrossRefGoogle ScholarPubMed
Ramalho, R. and Guimarães, C. (2008). The role of adipose tissue and macrophages in chronic inflammation associated with obesity: clinical implications. Acta médica portuguesa 21, 489–496.Google Scholar
Rodríguez-Hernández, H., Simental-Mendía, L. E., Rodríguez-Ramírez, G. and Reyes-Romero, M. A. (2013). Obesity and inflammation: epidemiology, risk factors, and markers of inflammation. International Journal of Endocrinology 2013, 678159.CrossRefGoogle ScholarPubMed
Scarpellini, E. and Tack, J. (2012). Obesity and metabolic syndrome: an inflammatory condition. Digestive Diseases (Basel, Switzerland) 30, 148–153.CrossRefGoogle ScholarPubMed
Siriwardhana, N., Kalupahana, N. S., Cekanova, M., LeMieux, M., Greer, B. and Moustaid-Moussa, N. (2013). Modulation of adipose tissue inflammation by bioactive food compounds. Journal of Nutritional Biochemistry 24, 613–623.CrossRefGoogle ScholarPubMed
Stäger, S. and Rafati, S. (2012). CD8+ T cells in Leishmania infections: friends or foes? Frontiers in Immunology 3, 1–8.CrossRefGoogle ScholarPubMed
Terrazas, C., Varikuti, S., Kimble, J., Moretti, E., Boyaka, P. N. and Satoskar, A. R. (2015). IL-17A promotes susceptibility during experimental visceral leishmaniasis caused by Leishmania donovani . FASEB Journal 1–9.Google ScholarPubMed
Vouldoukis, I., Becherel, P. A., Riveros-Moreno, V., Arock, M., Da Silva, O., Debre, P., Mazier, D. and Mossalayi, M. D. (1997). Interleukin-10 and interleukin-4 inhibit intracellular killing of Leishmania infantum and Leishmania major by human macrophages by decreasing nitric oxide generation. European Journal of Immunology 27, 860–865.CrossRefGoogle ScholarPubMed
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L. and Ferrante, A. W. (2003). Obesity is associated with macrophage accumulation in adipose tissue. Journal of Clinical Investigation 112, 1796–1808.CrossRefGoogle ScholarPubMed
WHO Technical Report Series (2010). Control of the leishmaniasis: report of a meeting of the WHO Expert Committee on the Control of Leishmaniases, Geneva, 22–26 March 2010. World Health Organization Technical Report Series, Vol. 949, 202.Google Scholar
Wolf, A. M., Wolf, D., Rumpold, H., Enrich, B. and Tilg, H. (2004). Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes. Biochemical and Biophysical Research Communications 323, 630–635.CrossRefGoogle ScholarPubMed
Yadav, A., Amit, A., Chaudhary, R., Chandel, A. S., Mahantesh, V., Suman, S. S., Singh, S. K., Dikhit, M. R., Ali, V., Rabidas, V., Pandey, K., Kumar, A., Das, P. and Bimal, S. (2015). Leishmania donovani: impairment of the cellular immune response against recombinant ornithine decarboxylase protein as a possible evasion strategy of Leishmania in visceral leishmaniasis. International Journal for Parasitology 45, 33–42.CrossRefGoogle ScholarPubMed
Yang, H., Youm, Y.-H., Vandanmagsar, B., Ravussin, A., Gimble, J. M., Greenway, F., Stephens, J. M., Mynatt, R. L. and Dixit, V. D. (2010). Obesity increases the production of proinflammatory mediators from adipose tissue T cells and compromises TCR repertoire diversity: implications for systemic inflammation and insulin resistance. Journal of immunology (Baltimore, Md.: 1950) 185, 1836–1845.CrossRefGoogle ScholarPubMed
Yang, Z.-H., Miyahara, H., Takeo, J. and Katayama, M. (2012). Diet high in fat and sucrose induces rapid onset of obesity-related metabolic syndrome partly through rapid response of genes involved in lipogenesis, insulin signalling and inflammation in mice. Diabetology & Metabolic Syndrome 4, 32.CrossRefGoogle ScholarPubMed
Zhang, A. J. X., To, K. K. W., Li, C., Lau, C. C. Y., Poon, V. K. M., Chan, C. C. S., Zheng, B. J., Hung, I. F. N., Lam, K. S. L., Xu, A. and Yuen, K. Y. (2013). Leptin mediates the pathogenesis of severe 2009 pandemic influenza A(H1N1) infection associated with cytokine dysregulation in mice with diet-induced obesity. Journal of Infectious Diseases 207, 1270–1280.CrossRefGoogle ScholarPubMed
Zijlstra, E. E., Musa, A. M., Khalil, E. A. G., El Hassan, I. M. and El-Hassan, A. M. (2003). Post-kala-azar dermal leishmaniasis. Lancet Infectious Diseases 3, 87–98.CrossRefGoogle ScholarPubMed