Histopathology,humoral and cellular immune response in the murine model of Leishmania (Viannia) shawi |
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| Authors: | Luiz Felipe Domingues Passero Cláudia Marques Inês Vale-Gato Carlos Eduardo Pereira Corbett Márcia Dalastra Laurenti Gabriela Santos-Gomes |
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| Institution: | 1. Laboratorio Patologia de Moléstias Infecciosas, Faculdade de Medicina da Universidade de São Paulo, Brazil. Av. Dr. Arnaldo, 455, São Paulo, Brazil;2. UEI de Leishmanioses, Centre for Malaria and Tropical Diseases Associated Laboratoire, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira, 96, 1349-008, Lisboa, Portugal;1. Unidade de Ensino e Investigação de Parasitologia Médica, Centro de Malária e Outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa, Rua da Junqueira 100, 1349-008 Lisboa, Portugal;2. IBMC—Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal;3. ICBAS–Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Largo Prof. Abel Salazar 2, 4099-003 Porto, Portugal;4. CIISA, Faculdade de Medicina Veterinária, Universidade Técnica de Lisboa, Av. Universidade Técnica, 1300-477 Lisboa, Portugal;5. Departamento de Imunologia, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo dos Mártires de Pátria, Lisboa, Portugal;1. Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisboa, Portugal;2. CIISA, Faculdade de Medicina Veterinária, Universidade de Lisboa, Av. Universidade Técnica, 1300-477 Lisboa, Portugal;3. IPST-Instituto Português do Sangue e da Transplantação - Centro do sangue e da transplantação de Lisboa, Portugal;4. Laboratory of Pathology of Infectious Diseases (LIM50), Department of Pathology, Medical School of São Paulo University, Brazil;5. I3S, Instituto de Investigação e Inovação em Saúde, IBMC, Instituto de Biologia Molecular e Celular and ICBAS, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal;1. Laboratório de Patologia Aplicada (LApap), College of Veterinary Medicine, UNES—Univ Estadual Paulista, Rua Clóvis Pestana, 793 Araçatuba/SP, CEP: 16050-680, Brazil;2. Laboratoire des Processus Infectieux à Trypanosomatidés, Département Infection et Epidemiologie, Institut Pasteur, 25-28 Rue du Dr Roux, 75724 Paris Cedex 15, France;3. College of Veterinary Medicine, UNESP—Univ Estadual Paulista, Rua Clóvis Pestana, 793 Araçatuba/SP, CEP: 16050-680, Brazil;1. Parasitology Laboratory, Section for Microbiology, Immunology and Parasitology, Department of Food Safety and Infection Biology, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, P.O. Box 8146 Dep, N-0033 Oslo, Norway;2. Alere A.S., Oslo, Norway;3. Norwegian Kennel Club and Norwegian University of Life Sciences, Faculty of Veterinary Medicine and Biosciences, Department of Companion Animal Clinical Sciences, P.O. Box 8146 Dep, N-0033 Oslo, Norway;4. United States Department of Agriculture, Agricultural Research Service, Beltsville Agricultural Research Center, Animal Parasitic Diseases Laboratory, Building 1001, BARC-East, Beltsville, MD 20705-2350, USA;1. Laboratory of Pathology of Infectious Diseases (LIM50), Department of Pathology, Medical School of São Paulo University, Av. Dr. Arnaldo, 455. Cerqueira César, São Paulo, 01246-903, SP, Brazil;2. Center of Natural Sciences and Humanities, Federal University of ABC, Santo Andre, São Paulo, 09210-180, Brazil;3. Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa, Rua da Junqueira 100, 1349-008 Lisboa, Portugal;4. Departamento de Análises Clínicas e Toxicológicas, Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Rua General Gustavo Cordeiro de Farias, 384, 59012-570 Natal, Brazil;5. São Paulo State University (Unesp), Institute of Biosciences, São Vicente, Praça Infante Dom Henrique, s/n, 11330-900 São Vicente, SP, Brazil |
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| Abstract: | Leishmania (Viannia) shawi was recently characterized and few studies concerning modifications in cellular and humoral immune responses in experimental leishmaniasis have been conducted. In this work, immunopathological changes induced by L. shawi in chronically infected BALB/c mice were investigated. Infected BALB/c mice developed increased lesion size associated with strong inflammatory infiltrate diffusely distributed in the dermis, with highly infected macrophages. The humoral immune response was predominantly directed toward the IgG1 isotype. The functional activity of CD4+ and CD8+ T cells showed significantly increased TNF-α mRNA levels associated with reduced IFN-γ expression by CD4+ T cells and the double negative (dn) CD4CD8 cell subset. High IL-4 levels expressed by CD8+ T cells and dnCD4CD8 and TGF-β by CD4+ and CD8+ T cells were detected, while IL-10 was highly expressed by all three cell subpopulations. Taken together, these results show an evident imbalance between TNF-α and IFN-γ that is unfavorable to amastigote replication control. Furthermore, L. shawi seems to regulate different cell populations to express deactivating cytokines to avoid its own destruction. This study indicates BALB/c mice as a potentially good experimental model for further studies on American cutaneous leishmaniosis caused by L. shawi. |
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