Article
Innate immune receptors over expression correlate with chronic chagasic cardiomyopathy and digestive damage in patients
Registro en:
PEREIRA, Nathalie de Sena; et al. Innate immune receptors over expression correlate with chronic chagasic cardiomyopathy and digestive damage in patients. PLoS Negl Trop Dis., v.12, n.7, e0006589, 21p, July 2018.
1935-2727
1935-2735
Autor
Pereira, Nathalie de Sena
Queiroga, Tamyres Bernadete Dantas
Nunes, Daniela Ferreira
Andrade, Cléber de Mesquita
Nascimento, Manuela Sales Lima
Matta, Maria Adelaide do Valle
Câmara, Antônia Cláudia Jácome da
Galvão, Lúcia Maria da Cunha
Guedes, Paulo Marcos Matta
Chiari, Egler
Resumen
Chronic chagasic cardiomyopathy (CCC) is observed in 30% to 50% of the individuals
infected by Trypanosoma cruzi and heart failure is the important cause of death among
patients in the chronic phase of Chagas disease. Although some studies have elucidated
the role of adaptive immune responses involving T and B lymphocytes in cardiac pathogenesis,
the role of innate immunity receptors such as Toll-like receptors (TLRs) and Nod-like
receptors (NLRs) in CCC pathophysiology has not yet been determined. In this study, we
evaluated the association among innate immune receptors (TLR1-9 and nucleotide-binding
domain-like receptor protein 3/NLRP3), its adapter molecules (Myd88, TRIF, ASC and caspase-
1) and cytokines (IL-1β, IL-6, IL-12, IL-18, IL-23, TNF-α, and IFN-β) with clinical manifestation,
digestive and cardiac function in patients with different clinical forms of chronic
Chagas disease. The TLR8 mRNA expression levels were enhanced in the peripheral blood
mononuclear cells (PBMC) from digestive and cardiodigestive patients compared to indeterminate
and cardiac patients. Furthermore, mRNA expression of IFN-β (cytokine produced
after TLR8 activation) was higher in digestive and cardiodigestive patients when compared
to indeterminate. Moreover, there was a positive correlation between TLR8 and IFN-β
mRNA expression with sigmoid and rectum size. Cardiac and cardiodigestive patients presented
higher TLR2, IL-12 and TNF-α mRNA expression than indeterminate and digestive
patients. Moreover, cardiac patients also expressed higher levels of NLRP3, ASC and IL-1β
mRNAs than indeterminate patients. In addition, we showed a negative correlation among
TLR2, IL-1β, IL-12 and TNF-α levels with left ventricular ejection fraction, and positive correlation
between NLRP3 with cardiothoracic index, and TLR2, IL-1β and IL-12 with left ventricular
mass index. Together, our data suggest that high expression of innate immune.receptors in cardiac and digestive patients may induce an enhancement of cytokine expression
and participate of cardiac and digestive dysfunction.