Activation of cord blood myeloid dendritic cells by Trypanosoma cruzi and parasite-specific antibodies, proliferation of CD8+ T cells, and production of IFN-γ

Abstract

We previously reported that Trypanosoma cruzi, the agent of Chagas disease, induces in congenitally infected fetuses a strong, adult-like parasite-specific CD8(+) T cell response producing IFN-γ (Hermann et al. in Blood 100:2153-2158, 2002). This suggests that the parasite is able to overcome the immaturity of neonatal antigen presenting cells, an issue which has not been previously addressed. We therefore investigated in vitro the ability of T. cruzi to activate cord blood DCs and compared its effect to that on adult cells. We show that T. cruzi induces phenotypic maturation of cord blood CD11c(+) myeloid DCs (mDCs), by enhancing surface expression of CD40, CD80, and CD83, and that parasite-specific IgG purified from cord blood of neonates born to T. cruzi-infected mothers amplify such expression. CD83, considered as the best marker of mature DCs, reaches higher level on cord blood than on adult mDCs. Allo-stimulation experiments showed that T. cruzi-activated cord blood mononuclear cells enriched in DCs (eDCs) stimulate proliferation of cord blood and adult CD3(+) T cells to a similar extent. Of note, T. cruzi-activated eDCs from cord blood trigger more potent proliferation of CD8(+) than CD8(-) (mainly CD4(+)) adult T cells, a feature not observed with adult eDCs. T cell proliferation is associated with IFN-γ release and down-regulation of IL-13 production. These data show that T. cruzi potently activates human cord blood mDCs and endows eDCs to trigger CD8(+) T cell proliferation and favor type 1 immune response. Interestingly, maternal antibodies can strengthen the development of mature DCs that might contribute to overcome the immunological immaturity associated with early life.

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

“…The results obtained in the identiWed gated population are presented as percentage of cells expressing the analysed marker, and as MFI of the cell population, after having subtracted the value of the MFI obtained with the isotype-matched control mAb. The expression levels of co-stimulatory molecules on mDCs incubated with unlabelled or CSFE-labelled trypomastigotes were similar and as described previously [34], indicating that CSFE did not interfere with the process of activation or with analyses performed by Xow cytometry (data not shown).…”

“…In a recent work, we also reported that live T. cruzi parasites enhance expression of co-stimulatory surface molecules on cord blood myeloid dendritic cells (mDCs) and that T. cruzi-activated mononuclear cells from cord blood, containing activated mDCs, promote proliferation of CD8 + T cells and type 1-polarized response [34], whereas other studies showed that T. cruzi inhibits the response to lipopolysaccharide (LPS) of monocyte-derived DCs (MoDCs) from adult blood [48,49]. The present work aims to determine the susceptibility of mDCs and other leucocytes to T. cruzi infection and to decipher the role of extracellular versus intracellular, as well as live versus lysed parasites, in activation of cord blood mDCs.…”

“…The following monoclonal antibodies and their matched isotype controls were used: lineage cocktail 1-FITC ("Lin1", containing Ab against CD3, CD14, CD16, CD19, CD20 and Analyses were performed as previously described [34]. mDCs were deWned as HLA-DR + , lineage (lin ¡ ) and CD34 ¡ negative cells expressing CD11c, or as CD1c + CD19 ¡ cells when CFSE-labelled parasites were used.…”

“…Whole blood cell incubation with T. cruzi parasites Whole blood cells were cultured with T. cruzi parasites as previously described [34]. BrieXy, 2 mL of whole blood samples half-diluted in RPMI 1640 medium containing 2 mM L-glutamine, 25 mM HEPES, penicillin 100 U/mL and streptomycin 100 g/mL (Lonza, Verviers, Belgium) was incubated with 10 6 or 10 7 CSFE-labelled live parasites/ mL (i.e.…”

Mother-to-Child Transmission of Trypanosoma cruzi

“…The immunological state of the mother [6,[33][34][35] and fetus [16,[43][44][45][46] may be important for congenital transmission. Hermann et al [33] observed that decreased maternal immune response to parasitic antigens was associated with increased risk of congenital transmission.…”