Infecção do vírus dengue aumenta a citoadesão dos eritrócitos infectados com Plasmodium vivax

Abstract

Malaria and dengue are prevalent diseases in tropical and subtropical regions and are great importance in public health. In malaria, there is a phenomenon associated with pathogenicity called cytoadherence, in which parasite sequestration occurs to other organs of the body. Some endothelial cell receptors are involved in this process such as ICAM-1, PECAM-1, VCAM-1 and P-selectin. In endemic areas to the malarial parasite and dengue virus, simultaneous infections may occur. However, little is known about malaria and dengue coinfection in Brazil. None study has yet shown what occurs in cytoadhesion during dengue-malaria coinfection. Therefore, our objective was to observe whether the adhesion of Plasmodium vivax-infected erythrocytes (PviEs) increases in human hepatocarcinoma (HEP-G2) cells concomitantly infected with dengue. Dengue 4 viral stock (DENV4) was done on C6/36 cells and PviEs were enriched by Percoll gradient to be used in the HEP-G2 cell cytoadhesion assay. Our results showed that HEP-G2 cells express the adhesion molecule ICAM-1, but not PECAM-1 and VCAM-1, while A549 cells do not express the molecules. We also showed that DENV4 replicates in HEP-G2 cells and increased ICAM-1 expression in virus-infected cells after 4 days of infection. In addition, we observed that PviEs cytoadhesion increased after DENV4 infection. Trypsin treatment, degrading parasite proteins, decreased PviEs adhesion, while the presence of anti-Pv human serum was not protective against cytoadhesion. Use of the BX795 inhibitor reduced PviEs levels, unlike chloroquine. Finally, PviEs adhesion decreased 5.5-fold in HEP-G2 cells treated with the a-ICAM-1 antibody when compared to the without blocker control. These results demonstrate that PviEs cytoadhesion increases with a concomitant DENV infection and suggest further investigations into receptors and immune pathways involved in this phenomenon during dengue-malaria coinfection. This study also alerts us to greater attention to patients diagnosed with dengue or malaria monoinfection in endemic areas.