Galectin-3 and Chagas Disease–Associated Cardiomyopathy

To the Editor—We read with great interest the study by Pineda et al [1]. Using a murine model of Trypanosoma cruzi infection, the authors found that galectin-3 deficiency deregulates Toll-like receptor expression on antigen-presenting cells, transiently increases blood but not cardiac parasitism, and reduces cytokine production, myocardial inflammation, and fibrosis during infection. Because the results of this study can help broaden the understanding of the pathogenesis of Chagas disease, especially cardiomyopathy, we wish to provide perspective to these findings. Considering that, during T. cruzi infection, the installation of a predominantly T-helper type (Th1) proinflammatory pattern is essential for the control of parasite burden and organ parasitism [2, 3], it was an interesting but controversial finding that the remarkable antiinflammatory effect triggered by galectin-3 deficiency was accompanied by a similar degree of blood parasite clearance and cardiac parasitism. Even considering the authors' proposition that galectin-3 is not involved in acquired immunity, it is intriguing that galectin-3−/− mice can control systemic and cardiac parasitism in the same way as wild-type animals, despite marked deficits in pivotal recognition (by Toll-like receptors) and defense mechanisms (ie, cytokine and nitric oxide release) among innate response cells. This aspect is reinforced by the similar distribution of CD4+ and CD8+ T cells in cardiac tissue, dismissing a late compensatory effect mediated by these cells. Furthermore, it is also possible that B-cell expansion and parasite-specific antibody responses (which were not investigated) are insufficient to control parasitemia and parasitism, since acute T. cruzi infection has been reported to induce the expansion of B cells by parasite mitogens without necessarily generating a parasite-specific response [4]. The specific humoral response can be further impaired by disturbances in the early secretion of Th1 cytokines, which drives antibody production [4] and was drastically reduced by galectin-3 deficiency. Although these aspects remain poorly understood, considering that the immunosuppressant phenotype determined by galectin-3 deficiency surprisingly does not favor heart parasitism, the reduction of cardiac inflammation and fibrosis makes galectin-3 a potential molecular target in the therapeutic management of Chagas disease–associated cardiomyopathy. In Chagas disease, although the establishment of a proinflammatory response is essential to the control parasitism, intense myocarditis is often associated with a high mortality rate during the acute phase of T. cruzi infection or with intense fibrosis and cardiac insufficiency during the chronic phase [2, 3]. Since Chagas disease–associated cardiomyopathy yields a worse prognosis than noninflammatory cardiomyopathies, and because the main difference between the natural evolution of these pathologies is the presence of inflammatory infiltrate in the cardiac tissue of chagasic patients [3, 5], interventions that modulate the inflammatory process, although not always with an antiparasitic effect, could mitigate the severity and mortality of Chagas disease–associated cardiomyopathy. Financial support. This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (454901/2014-3 to R. D. N.) and the Fundação de Amparo à Pesquisa do Estado de Minas Gerais (APQ-02309-14 to R. D. N.). Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.