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REPEATED EXPOSURE TO LUTZOMYIA INTERMEDIA SAND FLY SALIVA INDUCES LOCAL EXPRESSION OF INTERFERON-INDUCIBLE GENES BOTH AT THE SITE OF INJECTION IN MICE AND IN HUMAN BLOOD
Leishmania braziliensis/imunologia
Psychodidae/imunologia
Saliva/imunologia
Animais
Brasil
Células Cultivadas
Feminino
Perfilação da Expressão Gênica
Humanos
Interferons/imunologia
Leucócitos Mononucleares/imunologia
Camundongos
Camundongos Endogâmicos BALB C
Reação em Cadeia da Polimerase em Tempo Real
10.1371/journal.pntd.0002627
Autor
Afiliación
University of Lausanne. Department of Biochemistry. WHO-Immunology Research and Training Center. Epalinges, Switzerland
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia (iii-INCT). Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / National Institute of Science and Technology in Tropical Diseases. CNPq. Salvador, BA, Brasil
University of Lausanne. Department of Biochemistry. WHO-Immunology Research and Training Center. Epalinges, Switzerland
Universidade Federal da Bahia.Complexo Hospitalar Hospital Universitário Prof. Edgard Santos. Departamento de Imunologia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia (iii-INCT). Salvador, BA, Brasil
University of Lausanne. Department of Biochemistry. WHO-Immunology Research and Training Center. Epalinges, Switzerland
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia (iii-INCT). Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / National Institute of Science and Technology in Tropical Diseases. CNPq. Salvador, BA, Brasil
University of Lausanne. Department of Biochemistry. WHO-Immunology Research and Training Center. Epalinges, Switzerland
Universidade Federal da Bahia.Complexo Hospitalar Hospital Universitário Prof. Edgard Santos. Departamento de Imunologia. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia (iii-INCT). Salvador, BA, Brasil
University of Lausanne. Department of Biochemistry. WHO-Immunology Research and Training Center. Epalinges, Switzerland
Resumen en ingles
During a blood meal, Lutzomyia intermedia sand flies transmit Leishmania braziliensis, a parasite causing tegumentary leishmaniasis. In experimental leishmaniasis, pre-exposure to saliva of most blood-feeding sand flies results in parasite establishment in absence of any skin damages in mice challenged with dermotropic Leishmania species together with saliva. In contrast, pre-immunization with Lu. intermedia salivary gland sonicate (SGS) results in enhanced skin inflammatory exacerbation upon co-inoculation of Lu. intermedia SGS and L. braziliensis. These data highlight potential unique features of both L. braziliensis and Lu. intermedia. In this study, we investigated the genes modulated by Lu. intermedia SGS immunization to understand their potential impact on the subsequent cutaneous immune response following inoculation of both SGS and L. braziliensis. The cellular recruitment and global gene expression profile was analyzed in mice repeatedly inoculated or not with Lu. intermedia. Microarray gene analysis revealed the upregulation of a distinct set of IFN-inducible genes, an immune signature not seen to the same extent in control animals. Of note this INF-inducible gene set was not induced in SGS pre-immunized mice subsequently co-inoculated with SGS and L. braziliensis. These data suggest the parasite prevented the upregulation of this Lu. intermedia saliva-related immune signature. The presence of these IFN-inducible genes was further analyzed in peripheral blood mononuclear cells (PBMCs) sampled from uninfected human individuals living in a L. braziliensis-endemic region of Brazil thus regularly exposed to Lu. intermedia bites. PBMCs were cultured in presence or absence of Lu. intermedia SGS. Using qRT-PCR we established that the IFN-inducible genes induced in the skin of SGS pre-immunized mice, were also upregulated by SGS in PBMCs from human individuals regularly exposed to Lu. intermedia bites, but not in PBMCs of control subjects. These data demonstrate that repeated exposure to Lu. intermedia SGS induces the expression of potentially host-protective IFN-inducible genes.
DeCS
Interações Hospedeiro-ParasitaLeishmania braziliensis/imunologia
Psychodidae/imunologia
Saliva/imunologia
Animais
Brasil
Células Cultivadas
Feminino
Perfilação da Expressão Gênica
Humanos
Interferons/imunologia
Leucócitos Mononucleares/imunologia
Camundongos
Camundongos Endogâmicos BALB C
Reação em Cadeia da Polimerase em Tempo Real
Editor
Public Library of Science
Referencia
WEINKOPFF, T. et al. Repeated exposure to Lutzomyia intermedia sand fly saliva induces local expression of interferon-inducible genes both at the site of injection in mice and in human blood. PLoS Neglected Tropical Diseases, v. 8, n. 1, p. e2627, 2014.ISSN
1935-273510.1371/journal.pntd.0002627
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