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

Thaisa Lucas Sandri; Fabiana Antunes Andrade; Kárita Cláudia Freitas Lidani; Elias Einig; Angelica Beate Winter Boldt; Benjamin Mordmüller; Meral Esen; Iara J Messias-Reason

doi:10.1371/journal.pntd.0007324

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

PLoS Negl Trop Dis. 2019 Apr 17;13(4):e0007324. doi: 10.1371/journal.pntd.0007324. eCollection 2019 Apr.

Authors

Thaisa Lucas Sandri^{1

2}, Fabiana Antunes Andrade², Kárita Cláudia Freitas Lidani², Elias Einig¹, Angelica Beate Winter Boldt^{2

3}, Benjamin Mordmüller¹, Meral Esen¹, Iara J Messias-Reason²

Affiliations

¹ Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.
² Laboratory of Molecular Immunopathology, Department of Clinical Pathology, Federal University of Paraná, Curitiba, Brazil.
³ Laboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná, Curitiba, Brazil.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Brazil
Case-Control Studies
Chagas Disease / genetics*
Chagas Disease / physiopathology*
Collectins / blood
Collectins / genetics*
Epistasis, Genetic*
Female
Genetic Predisposition to Disease
Haplotypes
Humans
Male
Mannose-Binding Protein-Associated Serine Proteases / genetics*
Middle Aged
Polymorphism, Single Nucleotide

Substances

Colec11 protein, human
Collectins
MASP2 protein, human
Mannose-Binding Protein-Associated Serine Proteases

Grants and funding

The authors gratefully acknowledge financial support for this study from CAPES (Coordenação de Aperfeiçoamento de Pessoal Superior), CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), Fundação Araucária (PPSUS-01/2016). The authors also acknowledge support by Deutsche Forschungsgemeinschaft and Open Access Publishing Fund of University of Tübingen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.