Human collectin-11 (COLEC11) and its synergic genetic interaction with MASP2 are associated with the pathophysiology of Chagas Disease.

Authors:
Thaisa Lucas Sandri
Thaisa Lucas Sandri
Laboratory of Molecular Immunopathology
Fabiana Antunes Andrade
Fabiana Antunes Andrade
Laboratory of Molecular Immunopathology
Benjamin Mordmuller
Benjamin Mordmuller
Eberhard Karls Universität Tübingen
Meral Esen
Meral Esen
Institute of Tropical Medicine
Antwerpen | Belgium
Iara J Messias-Reason
Iara J Messias-Reason
Federal University of Paraná
Brazil

PLoS Negl Trop Dis 2019 Apr 17;13(4):e0007324. Epub 2019 Apr 17.

Laboratory of Molecular Immunopathology, Department of Clinical Pathology, Federal University of Paraná, Curitiba, Brazil.

Chagas Disease (CD) is an anthropozoonosis caused by Trypanosoma cruzi. With complex pathophysiology and variable clinical presentation, CD outcome can be influenced by parasite persistence and the host immune response. Complement activation is one of the primary defense mechanisms against pathogens, which can be initiated via pathogen recognition by pattern recognition molecules (PRMs). Collectin-11 is a multifunctional soluble PRM lectin, widely distributed throughout the body, with important participation in host defense, homeostasis, and embryogenesis. In complex with mannose-binding lectin-associated serine proteases (MASPs), collectin-11 may initiate the activation of complement, playing a role against pathogens, including T. cruzi. In this study, collectin-11 plasma levels and COLEC11 variants in exon 7 were assessed in a Brazilian cohort of 251 patients with chronic CD and 108 healthy controls. Gene-gene interactions between COLEC11 and MASP2 variants were analyzed. Collectin-11 levels were significantly decreased in CD patients compared to controls (p<0.0001). The allele rs7567833G, the genotypes rs7567833AG and rs7567833GG, and the COLEC11*GGC haplotype were related to T. cruzi infection and clinical progression towards symptomatic CD. COLEC11 and MASP2*CD risk genotypes were associated with cardiomyopathy (p = 0.014; OR 9.3, 95% CI 1.2-74) and with the cardiodigestive form of CD (p = 0.005; OR 15.2, 95% CI 1.7-137), suggesting that both loci act synergistically in immune modulation of the disease. The decreased levels of collectin-11 in CD patients may be associated with the disease process. The COLEC11 variant rs7567833G and also the COLEC11 and MASP2*CD risk genotype interaction were associated with the pathophysiology of CD.

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http://dx.plos.org/10.1371/journal.pntd.0007324
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http://dx.doi.org/10.1371/journal.pntd.0007324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488100PMC
April 2019
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References

(Supplied by CrossRef)
Chagas disease
A Rassi et al.
Lancet 2010
Chagas disease in Latin America: an epidemiological update based on 2010 estimates
Wkly Epidemiol Rec Relev épidémiologique Hebd 2015
Chagas disease cardiomyopathy: Immunopathology and genetics
E Cunha-Neto et al.
Mediators of Inflammation 2014
Pathogenesis of chronic Chagas heart disease
JA Marin-Neto et al.
Circulation 2007
The Complement System: A Prey of Trypanosoma cruzi
KCF Lidani et al.
Front Microbiol 2017

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