The Role of Sialic Acid-Binding Receptors (Siglecs) in the Immunomodulatory Effects of Trypanosoma cruzi Sialoglycoproteins on the Protective Immunity of the Host
Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and is an important endemic infection in Latin America. Lately, it has also become a health concern in the United States and Europe. Most of the immunomodulatory mechanisms associated with this parasitic infection have been attributed to mucin-like molecules on the T. cruzi surface. Mucins are high molecular weight glycoproteins that are involved in regulating diverse cellular activities in both normal and pathological conditions. In Trypanosoma cruzi infection, the parasite-derived mucins are the main acceptors of sialic acid and it has been suggested that they play a role in various host-parasite interactions during the course of Chagas disease. Recently, we have presented evidence that sialylation of the mucins is required for the inhibitory effects on CD4+ T cells. In what follows we propose that signaling via sialic acid-binding Ig-like lectin receptors for these highly sialylated structures on host cells contributes to the arrest of cell cycle progression in the G1 phase and may allow the parasite to modulate the immune system of the host. 1. Trypanosoma cruzi Infection and the Immunopathology of Chagas Disease Chagas’ disease or American trypanosomiasis is a tropical parasitic illness affecting nearly 20 million people in the Americas [1, 2]. The disease is caused by the protozoan flagellated parasite Trypanosoma cruzi, transmitted to humans by haematophagous insects known as triatomines (Reduviidae family). The complex life cycle of T. cruzi includes epimastigote and metacyclic trypomastigote stages in the insect vector and bloodstream trypomastigote and intracellular amastigotes in the vertebrate host [3]. In the latter, the Trypanosoma cruzi infects several cell types, including monocytes, fibroblasts, endothelial cells, and muscle cells [4–9]. This capacity to invade a wide range of host cells is associated with increased tissue inflammation and evokes a strong immunological response. This host protective response results from host tissue damage due to increased infiltration of leukocytes to the inflammatory sites, producing proinflammatory mediators, including cytokines, chemokines, and nitric oxide, among other factors [10–14]. Approximately 30% of infected patients develop symptoms of the disease in their lifetime; these include cardiomyopathy, neuropathies, and dilatation of the colon or esophagus [15]. The pathogenesis of Chagas disease is controversial and distinct hypotheses have been considered, including autoimmune manifestations and parasite-driven tissue damage
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