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

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

doi:10.3389/fcimb.2020.00285

Abstract

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 Trypanosoma cruzi 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 T. cruzi infection.

Highlights

Galectins (Gals) bind β-galactosides via carbohydrate recognition domains and modulate immune cell responses through several mechanisms
To analyze the role of Gal-8 in the context of parasite infection, we infected B6 and Gal-8-deficient mice with the Trypanosoma cruzi Ac strain that leads to chronic infection in this model (Risso et al, 2004)
To comparatively assess the inflammatory response induced by T. cruzi infection, cardiac tissues from infected wild-type (iWT), iGal-8KO, and non-infected control mice were analyzed by histopathology

Summary

Introduction

Galectins (Gals) bind β-galactosides via carbohydrate recognition domains and modulate immune cell responses through several mechanisms. Galectin-8 (Gal-8) has been involved in homeostatic and pathological processes. It regulates cytokine production, cellular adhesion, apoptosis, chemotaxis, endocytosis, differentiation, and migration in a wide range of cell types including immune cells (Elola et al, 2014). Gal-8 induces firm but reversible adhesion of peripheral neutrophils to endothelial cells (Nishi et al, 2003). Together with platelet activation (Romaniuk et al, 2010), these processes suggest a potential pro-inflammatory role for Gal-8. With the use of an in vitro approach, Gal-8 was found to be involved in preaparesis induction, a cell removal mechanism that prevents local inflammation and systemic immune response activation. Cells undergoing preaparesis or apoptosis is signaled by expose phosphatidylserine (PS) as signals for phagocytosis, but preaparesis only removes viable neutrophils (Stowell et al, 2008)

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