title: Human leucocyte antigen-G (HLA-G) and its murine functional homolog Qa2 in the Trypanosoma cruzi Infection.
abstract: Genetic susceptibility factors, parasite strain, and an adequate modulation of the immune system seem to be crucial for disease progression after Trypanosoma cruzi infection. HLA-G and its murine functional homolog Qa2 have well-recognized immunomodulatory properties. We evaluated the HLA-G 3' untranslated region (3'UTR) polymorphic sites (associated with mRNA stability and target for microRNA binding) and HLA-G tissue expression (heart, colon, and esophagus) in patients presenting Chagas disease, stratified according to the major clinical variants. Further, we investigated the transcriptional levels of Qa2 and other pro- and anti-inflammatory genes in affected mouse tissues during T. cruzi experimental acute and early chronic infection induced by the CL strain. Chagas disease patients exhibited differential HLA-G 3'UTR susceptibility allele/genotype/haplotype patterns, according to the major clinical variant (digestive/cardiac/mixed/indeterminate). HLA-G constitutive expression on cardiac muscle and colonic cells was decreased in Chagasic tissues; however, no difference was observed for Chagasic and non-Chagasic esophagus tissues. The transcriptional levels of Qa2 and other anti and proinflammatory (CTLA-4, PDCD1, IL-10, INF-γ, and NOS-2) genes were induced only during the acute T. cruzi infection in BALB/c and C57BL/6 mice. We present several lines of evidence indicating the role of immunomodulatory genes and molecules in human and experimental T. cruzi infection.
authors: Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors: Fabrício C
authors: FC
authors: Dias
authors: Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors: Celso T
authors: CT
authors: Mendes-Junior
authors: Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors: Maria C
authors: MC
authors: Silva
authors: Departamento de Morfologia, Fisiologia e Patologia Básica, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors: Fabrine S M
authors: FS
authors: Tristão
authors: Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors: Renata
authors: R
authors: Dellalibera-Joviliano
authors: CEA, Institute of Emerging Diseases and Innovative Therapies, Research Division in Hematology and Immunology, Saint-Louis Hospital, 1 Avenue Claude Vellefaux, 75475 Paris, France.
authors: Philippe
authors: 0000-0002-2868-7401
authors: P
authors: Moreau
authors: Departamento de Patologia e Medicina Legal, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors: Edson G
authors: EG
authors: Soares
authors: Departamento de Patologia e Medicina Legal, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors: Jean G
authors: JG
authors: Menezes
authors: Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors: André
authors: A
authors: Schmidt
authors: Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors: Roberto O
authors: RO
authors: Dantas
authors: Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors: José A
authors: JA
authors: Marin-Neto
authors: Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors: João S
authors: JS
authors: Silva
authors: Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil ; Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.
authors: Eduardo A
authors: EA
authors: Donadi
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000378:metabolism* / Q000469:parasitology*; D060005:Genotyping Techniques; D059951:HLA-G Antigens / Q000235:genetics / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000472:pathogenicity*
chemical_list: D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; C032907:Q surface antigens; D016753:Interleukin-10