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It is also a predisposing factor for infectious diseases, increasing mortality rates. Moreover, diet-induced obesity can cause metabolic fluctuations that affect macrophage differentiation in various organs. In this sense, we investigated how bone marrow-derived macrophages and tissue-resident macrophages in the skin, which have been differentiated in a host with metabolic syndrome and with previous inflammatory burden, respond to Leishmania major infection. Our findings suggest that bone marrow-derived macrophages from obese C57BL\/6 mice, even when cultivated in vitro with inflammatory stimuli, are more susceptible to L. major. These macrophages produce less tumor necrosing factor (TNF) and nitric oxide (NO) and show higher arginase activity. Furthermore, obese mice infected with an intermediate dose of L. major in the skin had more severe lesions when analyzed for ulceration, diameter, thickness, and parasite burden. The increase in lesion severity in obese mice was associated with a higher frequency of tissue-resident macrophages, which are less efficient in killing parasites. We also used CCR2\u2212\/\u2212 mice, which predominantly have tissue-resident macrophages, and found that lesion resolution was delayed in association with CCR2 deficiency. Additionally, obesity potentiated tissue damage, resulting in higher frequency of tissue-resident macrophages. Our results demonstrate that obesity can alter macrophage responses to infection, leading to increased susceptibility to L. major and more severe cutaneous leishmaniasis. These findings may have important implications for managing obesity-related infections and the development of new therapies for cutaneous leishmaniasis.<\/jats:p>","DOI":"10.1093\/jleuko\/qiae171","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T20:09:30Z","timestamp":1725048570000},"page":"1372-1384","source":"Crossref","is-referenced-by-count":4,"title":["Obesity alters the macrophages\u2019 response to <i>Leishmania major<\/i> in C57BL\/6 mice"],"prefix":"10.1093","volume":"116","author":[{"given":"Vinicius Dantas","family":"Martins","sequence":"first","affiliation":[{"name":"Postgraduate Program in Biochemistry and Immunology, Biological Sciences Institution, Universidade Federal de Minas Gerais , Avenida Ant\u00f4nio Carlos, 6627, CEP 31270-672, Belo Horizonte ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Vaz","sequence":"additional","affiliation":[{"name":"Postgraduate Program in 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,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2048-0318","authenticated-orcid":false,"given":"Licia","family":"Torres","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Biochemistry and Immunology, Biological Sciences Institution, Universidade Federal de Minas Gerais , Avenida Ant\u00f4nio Carlos, 6627, CEP 31270-672, Belo Horizonte ,","place":["Brazil"]},{"name":"Postgraduate Program in Nutrition and Health, School of Nursing, Universidade Federal de Minas Gerais , Avenida Alfredo Balena, 190, CEP 30130-100, Belo Horizonte ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos Felipe Andrade","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Biochemistry and Immunology, Biological Sciences Institution, Universidade Federal de Minas Gerais , Avenida Ant\u00f4nio Carlos, 6627, CEP 31270-672, Belo Horizonte 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