Mast cells in the colon of Trypanosoma cruzi-infected patients: are they involved in the recruitment, survival and/or activation of eosinophils?

Abstract

Megacolon is frequently observed in patients who develop the digestive form of Chagas disease. It is characterized by dilation of the rectum-sigmoid portion and thickening of the colon wall. Microscopically, the affected organ presents denervation, which has been considered as consequence of an inflammatory process that begins at the acute phase and persists in the chronic phase of infection. Inflammatory infiltrates are composed of lymphocytes, macrophages, natural killer cells, mast cells, and eosinophils. In this study, we hypothesized that mast cells producing tryptase could influence the migration and the activation of eosinophils at the site, thereby contributing to the immunopathology of the chronic phase. We seek evidence of interactions between mast cells and eosinophils through (1) evaluation of eosinophils, regarding the expression of PAR2, a tryptase receptor; (2) correlation analysis between densities of mast cells and eosinophils; and (3) ultrastructural studies. The electron microscopy studies revealed signs of activation of mast cells and eosinophils, as well as physical interaction between these cells. Immunohistochemistry and correlation analyses point to the participation of tryptase immunoreactive mast cells in the migration and/or survival of eosinophils at the affected organ.

Increased Duodenal Eosinophil Degranulation in Patients with Functional Dyspepsia: A Prospective Study

“…Mast cell is also a trigger for eosinophil migration into the gastrointestinal tract 36 . There is convincing evidence that mast cell tryptase activates eosinophils through PAR-2 receptor expressed on eosinophils 37 38 .…”

Mast Cell Coupling to the Kallikrein–Kinin System Fuels Intracardiac Parasitism and Worsens Heart Pathology in Experimental Chagas Disease

“…More recently, studies of the pathogenesis of anaphylaxis linked severe MC-mediated reactions to BK release via heparin-induced activation of the contact system ( 10 ). Given this precedent, and limited information about the pathogenic role of MCs in Chagas disease ( 49 , 50 ), we asked whether T. cruzi -induced inflammation was propagated via activation of the MC/KKS pathway. IVM in the HCP seemed to be an appropriate system to address this question because (i) MCs are predominantly positioned along arterioles of the HCP and respond to topically applied stimuli such as 48/80 ( 51 ), (ii) the pathogens are topically applied to the HCP ( 33 ), hence dispensing the use of needles—a procedure that causes bleeding and spurious KKS activation, and (iii) hamsters are susceptible to T. cruzi infection and exhibit a dilated chronic cardiomyopathy that closely resembles the human heart disease ( 52 ).…”

Biomarkers and Their Possible Functions in the Intestinal Microenvironment of Chagasic Megacolon: An Overview of the (Neuro)inflammatory Process

“…Moreover, tryptase was suggested to participate in the inflammatory cell transmigration process [150][151][152][153]. Lung allergy [154,155], psoriasis [156], asthma [157], and CD models [158] showed that this protease is a potential component in eosinophilic infiltration. The increased tryptase-IR MCs in the myenteric plexus and internal muscle layer were positively correlated with increased eosinophils in the same regions in Chagasic megacolon [158] and showed cell proximity under electron microscopy, suggesting a possible communication between MCs and eosinophils via PAR2.…”

“…Lung allergy [154,155], psoriasis [156], asthma [157], and CD models [158] showed that this protease is a potential component in eosinophilic infiltration. The increased tryptase-IR MCs in the myenteric plexus and internal muscle layer were positively correlated with increased eosinophils in the same regions in Chagasic megacolon [158] and showed cell proximity under electron microscopy, suggesting a possible communication between MCs and eosinophils via PAR2. The role of MCs-eosinophil communication during the T. cruzi infection is unknown, but MCs are believed to participate in eosinophil survival in Chagasic megacolon [158].…”