Trypanosoma cruzi activates cord blood myeloid dendritic cells independently of cell infection

Abstract

We recently showed that T. cruzi parasites enhance expression of co-stimulatory surface molecules on cord blood myeloid dendritic cells (mDCs). This study aims to gain insight into the role of live parasites and intracellular infection in mDC activation using CSFE-labelled parasites. First, we observed that only a low proportion of mDCs was infected by T. cruzi after overnight culture of whole blood samples and trypomastigotes, as compared with monocytes and granulocytes. Cord blood mDCs were also less infected than their adult counterpart. Second, expression levels of HLA-DR and co-stimulatory molecules CD80, CD83 and CD86 were similar on infected and uninfected mDCs. Parasite lysate also triggered mDCs phenotypic maturation of both cord and adult blood cells, though in a lower extent than live parasites. These results strongly support a central role for extracellular trypomastigotes in activation of mDCs when parasites are incubated with whole blood cells. However, viability of trypomastigotes was not absolutely required for mDC activation.

Response to Trypanosoma cruzi by Human Blood Cells Enriched with Dentritic Cells Is Controlled by Cyclooxygenase-2 Pathway

“…T. cruzi parasites also activates cord blood myeloid DCs, increasing the expression of CD40 and CD80 and promoting proliferation of CD8 + T cells and type-1-polarized response (Rodriguez et al, 2012a ). It was also demonstrated that T. cruzi lysate elicits myeloid DCs independently of infection (Rodriguez et al, 2012b ), a process recently revised by Gil-Jaramillo et al ( 2016 ).…”

The First Contact of Human Dendritic Cells With Trypanosoma cruzi Reveals Response to Virus as an Unexplored Central Pathway

“…Since control MoDCs presented a relatively high expression of typical activation markers, morphological change is a useful tool for assessing maturation of DCs (36,51,52). Using this approach, a high percentage of morphological changes was observed in the MoDCs, indicating bystander activation after contact with the parasite (65)(66)(67)(68), and a similar infection rate to those seen in other studies (39,40). A mixed gene expression profile from bystander and infection activation in MoDCs is the expected scenario in the initial stage of natural infection when not every cell is infected or mature (35).…”

Dendritic Cells: A Double-Edged Sword in Immune Responses during Chagas Disease

“…In addition, they demonstrated that either infected mDCs or T. cruzi lysates co-incubated mDCs have a similar expression pattern of their surface molecules. The authors also showed that infection rate in mDCs is lower than in monocytes and granulocytes, maybe due to their enhanced capacity of phagocytosis when compared to mature DCs ( Rodriguez et al, 2012b ). Consistent with the results shown in murine model, modulation of DCs function varies according to T. cruzi strain.…”