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Dogs are considered the major domestic reservoir animals for leishmaniasis, and through their highly parasitized skin, they can serve as a source of infection for sandfly vectors. Therefore, studies of the skin parasite\u2013host relationship can contribute to the understanding of the infectious dissemination processes of parasites in the dermis and help to identify targets for diagnosis and treatment. Thus, the aim of this study was to evaluate the association of anatomical vascular differences and Leishmania-induced vascular morphological changes with clinical signs and parasite load by analyzing the ear and abdominal skin from dogs naturally infected with L. infantum. Paired samples of ear and abdominal skin from L. infantum-positive dogs (n = 26) were submitted for histological and immunohistochemistry analyses. The ear skin samples showed a more intense and more diffusely distributed granulomatous inflammatory reaction, a higher number and larger diameter of blood vessels, increased parasite load, higher expression of VEGF+ (vascular endothelial growth factor) and MAC 387+ (calprotectin) recently infiltrating cells, and more intense collagen disruption compared to the abdominal skin samples. Intracellular amastigotes were observed in blood vessels and inside endothelial cells and were diffusely distributed throughout the dermis in the ear skin samples. The NOS2\/MAC387+ cell ratio was lower in the ear skin samples than in those of the abdomen, suggesting that in the ear dermis, the inflammatory infiltrate was less capable of producing NO and thereby control the parasite load. Together, these findings indicate how parasites and immune cells are distributed in the skin and suggest an important role for dermal vascularization in cellular influx and thereby in parasite dissemination through the skin of naturally infected dogs.<\/jats:p>","DOI":"10.3390\/pathogens13050371","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T08:14:31Z","timestamp":1714464871000},"page":"371","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Anatomical Vascular Differences and Leishmania-Induced Vascular Morphological Changes Are Associated with a High Parasite Load in the Skin of Dogs Infected with Leishmania infantum"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1379-5549","authenticated-orcid":false,"given":"Francini N.","family":"Ribeiro","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Protozoologia, Instituto Oswaldo Cruz\u2014FIOCRUZ, Rio de Janeiro 21040-360, Brazil"},{"name":"Laborat\u00f3rio de Imunoparasitologia, Instituto Oswaldo Cruz\u2014FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7151-3354","authenticated-orcid":false,"given":"Tain\u00e3 L.","family":"de Souza","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Protozoologia, Instituto Oswaldo Cruz\u2014FIOCRUZ, Rio de Janeiro 21040-360, Brazil"},{"name":"Laborat\u00f3rio de Imunoparasitologia, Instituto Oswaldo Cruz\u2014FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1853-3449","authenticated-orcid":false,"given":"Rodrigo C.","family":"Menezes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa Cl\u00ednica em Dermatozoonoses em Animais Dom\u00e9sticos, Instituto Nacional de Infectologia Evandro Chagas\u2014FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Keidel","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa Cl\u00ednica em Dermatozoonoses em Animais Dom\u00e9sticos, Instituto Nacional de Infectologia Evandro Chagas\u2014FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Paulo R.","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Laboratorio de Medicina Experimental e Sa\u00fade, Instituto Oswaldo Cruz\u2014FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor J.","family":"da Silva","sequence":"additional","affiliation":[{"name":"Laboratorio de Medicina Experimental e Sa\u00fade, Instituto Oswaldo Cruz\u2014FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Pelajo-Machado","sequence":"additional","affiliation":[{"name":"Laboratorio de Medicina Experimental e Sa\u00fade, Instituto Oswaldo Cruz\u2014FIOCRUZ, Rio de Janeiro 21040-360, Brazil"},{"name":"Brazilian National Institute of Science and Technology on Neuroimmunomodulation, Instituto Oswaldo Cruz\u2014FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7188-251X","authenticated-orcid":false,"given":"Fernanda N.","family":"Morgado","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunoparasitologia, Instituto Oswaldo Cruz\u2014FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Porrozzi","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Protozoologia, Instituto Oswaldo Cruz\u2014FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,30]]},"reference":[{"key":"ref_1","first-page":"86","article-title":"The LeishVet Group. 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