Modulatory Effect of Trypanosoma cruzi Infective Stages in Different Dendritic Cell Populations in vitro

Abstract

Trypanosoma cruzi is a protozoan parasite that infects at least 7 million persons in the world (OMS, 2019). In endemic areas, infection normally occurs by vectorial transmission; however, outside, it normally happens by blood and includes congenital transmission. The persistence of T. cruzi during infection suggests the presence of immune evasion mechanisms and the modulation of the anti-parasite response to a profile incapable of eradicating the parasite. Dendritic cells (DCs) are a heterogeneous population of antigen-presenting cells (APCs) that patrol tissues with a key role in mediating the interface between the innate and adaptive immune response. Previous results from our lab and other groups have demonstrated that T. cruzi modulates the functional properties of DCs, in vitro and in vivo. During vectorial transmission, metacyclic (m) trypomastigotes (Tps) eliminated along with the insect feces reach the mucous membranes or injured skin. When transmission occurs by the hematic route, the parasite stage involved in the infection is the circulating or blood (b) Tp. Here, we studied in vitro the effect of both infective mTp and bTp in two different populations of DCs, bone marrow-derived DCs (BMDCs) and XS106, a cell line derived from epidermal DCs. Results demonstrated that the interaction of both Tps imparts a different effect in the functionality of these two populations of DCs, suggesting that the stage of T. cruzi and DC maturation status could define the immune response from the beginning of the ingress of the parasite, conditioning the course of the infection.

Early Immune Response Elicited by Different Trypanosoma cruzi Infective Stages

“…Recently, it has been reported that DCs with diverse origins, bone-marrow-derived DCs in steady state, and epidermicderived DCs responded differently to mTp and bTp infection and stimulation. In fact, not only the cell type but also the cellular activation status would condition APC response, in addition to the difference in the antigenic properties of the parasite (Gutierrez et al, 2020). As previously revised by Fernandes and Andrews (2012), trypomastigote-infective forms show big differences in molecular surface composition between mTp and bTp.…”

“…Recently, we have reported differences in the in vitro stimulatory capacity and infectivity of mTp and bTp in the culture with DCs from different origins (Gutierrez et al, 2020). Here, we compare some immunologic parameters after id injection of both infective stages in the experimental model.…”

“…In addition, our group has demonstrated the relevance of early monocyte mobilization at the site of the parasite entry and the relevance of this heterogeneous population, which includes Mo-DCs, at the first steps of infection (Poncini and Gonzaĺez Cappa, 2017). More recently, results obtained in vitro demonstrated that not only the parasite infective stage but also the origin and activation status would define the subset behavior of DCs (Gutierrez et al, 2020). The objective of the present work is to study the scope of the findings obtained in vitro in the experimental model of infection.…”

“…C3H/HeN and CF1 mice were maintained at the animal facilities of IMPaM UBA-CONICET, Facultad de Medicina, Universidad de Buenos Aires and bred ad libitum under sanitary barrier in specific pathogen-free conditions (Gutierrez et al, 2020).…”

“…Epimastigotes (epi) were routinely differentiated from bTp and cultured in vitro in liver infusion tryptose (LIT) medium at 27°C to the exponential phase of growth and centrifuged at 3,000×g for 15 min at 10°C (Isola et al, 1986). mTp were obtained by one round of differentiation from epi as described by Gutierrez et al (2020). After in vitro culture of 10 × 10 7 epi in 10% fetal bovine serum (FBS) LIT plus Grace's insect medium (MERC) and incubated at 27°C in tightly closed culture flasks, parasites were purified in DEAE column equilibrated with PBS-glucose (20%) at pH 8.2.…”