Human leucocyte antigen-G (HLA-G) and its murine functional homolog Qa2 in the Trypanosoma cruzi Infection.
Fabrício C DiasCelso T Mendes-JuniorMaria C SilvaFabrine S M TristãoRenata Dellalibera-JovilianoPhilippe MoreauEdson G SoaresJean G MenezesAndré SchmidtRoberto O DantasJosé A Marin-NetoJoão S SilvaEduardo A DonadiPublished in: Mediators of inflammation (2015)
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.
Keyphrases
- trypanosoma cruzi
- gene expression
- end stage renal disease
- genome wide
- endothelial cells
- ejection fraction
- newly diagnosed
- poor prognosis
- drug induced
- heart failure
- liver failure
- transcription factor
- binding protein
- prognostic factors
- left ventricular
- peritoneal dialysis
- induced apoptosis
- respiratory failure
- copy number
- intensive care unit
- dna methylation
- adipose tissue
- cell death
- bioinformatics analysis
- cell proliferation
- high glucose
- case report
- high speed
- atomic force microscopy