Transplant immunology · 2024
Expression patterns of Galectin-3 and NLRP3 in Chagas reactivation and graft damage in heart transplants.
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Gullo Caio E, Dos Santos Diego D, Corrêa Mab P, Gil Cristiane D, Bestetti Reinaldo B
Аннотация
OBJECTIVE: This study aimed to assess the expression patterns of galectin-3 (Gal-3) and NLRP3 in heart transplant recipients according to the presence of reactivated Trypanosoma cruzi infection or allograft rejection in Chagas and non-Chagas heart transplant recipients.
METHODS: Gal-3 and NLRP3 expression levels were analyzed in endomyocardial biopsies from 31 heart transplant recipients, including 16 patients with chronic Chagas disease (ChD) and 15 without ChD. Samples were evaluated during periods of graft rejection or ChD reactivation, characterized by intense myocardial cellular infiltrate, and after remission of the infiltrate, classified by histopathological severity. The transcriptional levels of genes encoding Gal-3, NLRP3, Asc, caspase-1, and IL-1β were identified using the GEO2T tool across different experimental conditions.
RESULTS: Gal-3 expression was lower in the myocardial infiltrate of ChD patients compared to non-ChD patients (p < 0.0001), whereas NLRP3 positivity was higher in ChD patients (p < 0.05). In a murine model of T. cruzi infection, elevated Gal-3 mRNA and NLRP3 inflammasome levels were observed in myocardial interstitial cells (p < 0.05). Peripheral blood mononuclear cells and cells from rodent cardiac allografts showed increased Gal-3 mRNA and NLRP3 levels compared to non-transplanted and rodent cardiac isografts (p < 0.001).
CONCLUSIONS: Our findings suggest that Gal-3 and NLRP3 may be important biomarkers for differentiating heart transplant recipients with and without ChD regarding the myocardial immunological processes.
METHODS: Gal-3 and NLRP3 expression levels were analyzed in endomyocardial biopsies from 31 heart transplant recipients, including 16 patients with chronic Chagas disease (ChD) and 15 without ChD. Samples were evaluated during periods of graft rejection or ChD reactivation, characterized by intense myocardial cellular infiltrate, and after remission of the infiltrate, classified by histopathological severity. The transcriptional levels of genes encoding Gal-3, NLRP3, Asc, caspase-1, and IL-1β were identified using the GEO2T tool across different experimental conditions.
RESULTS: Gal-3 expression was lower in the myocardial infiltrate of ChD patients compared to non-ChD patients (p < 0.0001), whereas NLRP3 positivity was higher in ChD patients (p < 0.05). In a murine model of T. cruzi infection, elevated Gal-3 mRNA and NLRP3 inflammasome levels were observed in myocardial interstitial cells (p < 0.05). Peripheral blood mononuclear cells and cells from rodent cardiac allografts showed increased Gal-3 mRNA and NLRP3 levels compared to non-transplanted and rodent cardiac isografts (p < 0.001).
CONCLUSIONS: Our findings suggest that Gal-3 and NLRP3 may be important biomarkers for differentiating heart transplant recipients with and without ChD regarding the myocardial immunological processes.