Journal Article

Anti-inflammatory Role of Galectin-8 During Trypanosoma cruzi Chronic Infection

Sanmarco, Liliana M., Pascuale, Carla A., Postan, Miriam, Aoki, Maria P., Leguizamón, María S., Bertelli, Adriano

2020

Overview

Galectins are animal lectins with high affinity for β-galactosides that drive the immune response through several mechanisms. In particular, the role of galectin-8 (Gal-8) in inflammation remains controversial. To analyze its role in a chronic inflammatory environment, we studied a murine model of infection. The parasite induces alterations that lead to the development of chronic cardiomyopathy and/or megaviscera in 30% of infected patients. The strong cardiac inflammation along with fibrosis leads to cardiomyopathy, the most relevant consequence of Chagas disease. By analyzing infected wild-type (iWT) and Gal-8-deficient (iGal-8KO) C57BL/6J mice at the chronic phase (4-5 months post-infection), we observed that the lack of Gal-8 favored a generalized increase in heart, skeletal muscle, and liver inflammation associated with extensive fibrosis, unrelated to tissue parasite loads. Remarkably, increased frequencies of neutrophils and macrophages were observed within cardiac iGal-8KO tissue by flow cytometry. It has been proposed that Gal-8, as well as other galectins, induces the surface expression of the inner molecule phosphatidylserine on activated neutrophils, which serves as an \"eat-me\" signal for macrophages, favoring viable neutrophil removal and tissue injury protection, a process known as preaparesis. We found that the increased neutrophil rates could be associated with the absence of Gal-8-dependent preaparesis, leading to a diminished neutrophil-clearing capability in macrophages. Thus, our results support that Gal-8 exerts an anti-inflammatory role in chronic infection.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Animal models / Animals / Anti-Inflammatory Agents / Antigens / Apoptosis / Cardiac muscle / Cardiomyopathy / Cellular and Infection Microbiology / Chagas Disease / Chronic infection / Connective tissue / Cytokines / Disease Models, Animal / Fibroblasts / Fibrosis / Flow cytometry / Galectins - immunology / Heart / Immune response / Infections / Inflammation / Laboratory animals / Lectins / Leukocytes (neutrophilic) / Macrophages / Mice / Mice, Inbred C57BL / Mice, Knockout / Musculoskeletal system / Neutrophils / Parasites / Phosphatidylserine / preaparesis / Protozoa / Skeletal muscle / Software / Trypanosoma cruzi / Tumor necrosis factor-TNF