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

• Published in: PLoS neglected tropical diseases 2019-04, Vol.13 (4), p.e0007324-e0007324
• Main Authors: Sandri, Thaisa Lucas, Andrade, Fabiana Antunes, Lidani, Kárita Cláudia Freitas, Einig, Elias, Boldt, Angelica Beate Winter, Mordmüller, Benjamin, Esen, Meral, Messias-Reason, Iara J
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biology and Life Sciences; Brazil; Carbohydrates; Cardiomyopathy; Care and treatment; Case-Control Studies; Chagas disease; Chagas Disease - genetics; Chagas Disease - physiopathology; Chronic illnesses; Cohorts; Collectins; Collectins - blood; Collectins - genetics; Complement activation; Defence mechanisms; Disease; Diseases; Embryogenesis; Embryonic growth stage; Epistasis; Epistasis, Genetic; Female; Funding; Genes; Genetic aspects; Genetic Predisposition to Disease; Genomes; Genotypes; Haplotypes; Homeostasis; Humans; Immune response; Immune system; Immunity; Immunomodulation; Interactions; Kidneys; Laboratories; Lectins; Levels; Male; Mannose; Mannose-binding lectin; Mannose-Binding Protein-Associated Serine Proteases - genetics; Mannose-binding protein-associated serine proteinase; MASP-2 protein; Medicine; Medicine and Health Sciences; Middle Aged; Molecules; Monosaccharides; Myocardial diseases; Parasites; Pathogenic microorganisms; Pathogens; Pathology; Pattern recognition; Persistence; Plasma levels; Polymorphism, Single Nucleotide; Proteases; Proteins; Risk factors; Serine; Tropical diseases; Trypanosoma cruzi; Vector-borne diseases
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0007324

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