Human Leucocyte Antigen-G (HLA-G) and Its Murine Functional Homolog Qa2 in theTrypanosoma cruziInfection

Author:

Dias Fabrício C.1,Mendes-Junior Celso T.2,Silva Maria C.3,Tristão Fabrine S. M.4,Dellalibera-Joviliano Renata5,Moreau Philippe6ORCID,Soares Edson G.7,Menezes Jean G.7,Schmidt André1,Dantas Roberto O.1,Marin-Neto José A.1,Silva João S.3,Donadi Eduardo A.13

Affiliation:

1. Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil

2. 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

3. Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil

4. 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

5. Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil

6. CEA, Institute of Emerging Diseases and Innovative Therapies, Research Division in Hematology and Immunology, Saint-Louis Hospital, 1 Avenue Claude Vellefaux, 75475 Paris, France

7. 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

Abstract

Genetic susceptibility factors, parasite strain, and an adequate modulation of the immune system seem to be crucial for disease progression afterTrypanosoma cruziinfection. HLA-G and its murine functional homolog Qa2 have well-recognized immunomodulatory properties. We evaluated theHLA-G3′ 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 duringT. cruziexperimental acute and early chronic infection induced by the CL strain. Chagas disease patients exhibited differentialHLA-G3′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 ofQa2and other anti and proinflammatory (CTLA-4, PDCD1, IL-10, INF-γ, andNOS-2) genes were induced only during the acuteT. cruziinfection in BALB/c and C57BL/6 mice. We present several lines of evidence indicating the role of immunomodulatory genes and molecules in human and experimentalT. cruziinfection.

Funder

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Publisher

Hindawi Limited

Subject

Cell Biology,Immunology

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