Implication of Apoptosis for the Pathogenesis of Trypanosoma cruzi Infection

Abstract

Apoptosis is induced during the course of immune response to different infectious agents, and the ultimate fate is the recognition and uptake of apoptotic bodies by neighboring cells or by professional phagocytes. Apoptotic cells expose specific ligands to a set of conserved receptors expressed on macrophage cellular surface, which are the main cells involved in the clearance of the dying cells. These scavenger receptors, besides triggering the production of anti-inflammatory factors, also block the production of inflammatory mediators by phagocytes. Experimental infection of mice with the parasite Trypanosoma cruzi shows many pathological changes that parallels the evolution of human infection. Leukocytes undergoing intense apoptotic death are observed during the immune response to T. cruzi in the mouse model of the disease. T. cruzi replicate intensely and secrete molecules with immunomodulatory activities that interfere with T cell-mediated immune responses and secretion of pro-inflammatory cytokine secretion. This mechanism of immune evasion allows the infection to be established in the vertebrate host. Under inflammatory conditions, efferocytosis of apoptotic bodies generates an immune-regulatory phenotype in phagocytes, which is conducive to intracellular pathogen replication. However, the relevance of cellular apoptosis in the pathology of Chagas’ disease requires further studies. Here, we review the evidence of leukocyte apoptosis in T. cruzi infection and its immunomodulatory mechanism for disease progression.

Lipid Bodies as Sites of Prostaglandin E2 Synthesis During Chagas Disease: Impact in the Parasite Escape Mechanism

“…During T. cruzi infection, the induction of apoptosis, especially of T and B lymphocytes ( Freire-de-Lima et al, 2000 ; DosReis, 2011 ) and neutrophils ( Magalhaes et al, 2017 ) represents an important mechanism that contributes to the parasite replication, due to the immunomodulatory effects on the host immune response ( Decote-Ricardo et al, 2017 ). Consequently, the efferocytosis or phagocytic clearance of these apoptotic cells by macrophages has profound consequences on innate and adaptive immune responses in inflamed tissues ( Elliott et al, 2017 ).…”

Antibody Repertoires Identify β-Tubulin as a Host Protective Parasite Antigen in Mice Infected With Trypanosoma cruzi

“…Production of antibodies against nuclear autoantigens correlates with increased apoptosis ( 37 ). Infection with T. cruzi exacerbates lymphocyte apoptosis ( 38 , 39 ), which is partially dependent on the Fas/FasL death pathway ( 40 – 43 ), but apoptosis is also increased in gld mice ( 40 ).…”

How to B(e)-1 Important Cell During Leishmania Infection

“…On the other hand, peritoneal B-1 cell-derived phagocytes (B-1CDP) are more susceptible than peritoneal macrophages to infection by L. major in vitro, with a higher percentage of infection, in terms of both the number of cells infected and the number of parasites per cell, as well as higher parasite proliferation ( Figure 1B) (Arcanjo et al, 2015). This was attributed to the fact that B-1CDP produce more IL-10, lipid bodies and PGE 2 endogenously than the macrophages ( Figure 1B), and when the B-1CDP are treated with anti-IL-10 or non-steroidal anti-inflammatory drugs that inhibit PGE 2 production these cells become as susceptible as macrophages (Freire- de-Lima et al, 2000de-Lima et al, , 2006Decote-Ricardo et al, 2017). Besides that, the treatment with non-steroidal anti-inflammatory drugs decreases the level of IL-10 produced by B-1CDP and it becomes the same as the level of IL-10 produced by macrophages (Arcanjo et al, 2015).…”