Early Immune Response Elicited by Different Trypanosoma cruzi Infective Stages

Abstract

Trypanosoma cruzi is a protozoan parasite that affects millions of people in Latin America. Infection occurs by vectorial transmission or by transfusion or transplacental route. Immune events occurring immediately after the parasite entrance are poorly explored. Dendritic cells (DCs) are target for the parasite immune evasion mechanisms. Recently, we have demonstrated that two different populations of DCs display variable activation after interaction with the two infective forms of the parasite: metacyclic or blood trypomastigotes (mTp or bTp) in vitro. The skin constitutes a complex network with several populations of antigen-presenting cells. Previously, we have demonstrated T. cruzi conditioning the repertoire of cells recruited into the site of infection. In the present work, we observed that mTp and bTp inoculation displayed differences in cell recruitment to the site of infection and in the activation status of APCs in draining lymph nodes and spleen during acute infection. Animals inoculated with mTp exhibited 100% of survival with no detectable parasitemia, in contrast with those injected with bTp that displayed high mortality and high parasite load. Animals infected with mTp and challenged with a lethal dose of bTp 15 days after primary infection showed no mortality and incremented DC activation in secondary lymphoid organs compared with controls injected only with bTp or non-infected mice. These animals also displayed a smaller number of amastigote nests in cardiac tissue and more CD8 T cells than mice infected with bTp. All the results suggest that both Tp infective stages induce an unequal immune response since the beginning of the infection.

Delayed Activation of T Cells at the Site of Infection Facilitates the Establishment of Trypanosoma cruzi in Both Naive and Immune Hosts

“…In the case of T. cruzi , these initial encounters occur at the site of parasite entry, which in naturally acquired infection is often the mucosa or breaks in the skin. Previous studies reported a relative lack of response to T. cruzi soon after infection in the skin, with no macroscopic evidence of inflammation up to 7 days postinfection and a modest influx of CD11b + leukocytes ( 18 – 20 ), although this pattern may be modified by the presence of insect feces or the infective parasite form ( 21 – 23 ). The response to T. cruzi gains momentum and ultimately constrains the infection, but this process is slower than might be expected ( 3 , 24 ) and, perhaps as a result, the infection rapidly disseminates systemically, where it is persistent ( 25 , 26 ).…”

Extracellular vesicles from Trypanosoma cruzi-dendritic cell interaction show modulatory properties and confer resistance to lethal infection as a cell-free based therapy strategy

“…RA bloodstream forms (Tp) were obtained from whole blood at the peak of parasitemia 7 days post-infection (dpi), thoroughly washed and purified by density gradient centrifugation as previously reported ( Poncini et al., 2008 ). For the lethal infection challenge, ten-to-twelve week old C57BL/6 male mice received intradermic (hindfoot) injection with 1000 parasites as previously described ( Poncini et al., 2015 ; Poncini et al, 2017 ; Gutierrez et al., 2021 ). Animal health condition, parasite load and mortality were periodically recorded.…”

“…At day 7 post EVs or PBS injection, animals were challenge with the lethal infection. To this end, ten-to-twelve week old C57BL/6 male mice received intradermic (id, hindfoot) injection with 1000 RA parasites ( Gutierrez et al., 2021 ). Experimental procedure included four to five animals per group depending on the experiment and was defined as: i) PBS, negative for infection; ii) PBS+Tp, positive for infection; iii) EVs DCs treatment+Tp; iv) EVs DCs+Tp treatment+Tp.…”

Fenofibrate Induces a Resolving Profile in Heart Macrophage Subsets and Attenuates Acute Chagas Myocarditis

“…For the acute myocarditis model, 8-week-old C57BL/6 male mice received an intradermal (hind footpad) injection with 3 × 10 3 trypomastigotes of the RA strain as previously described. 81 Randomly selected mice received a daily oral gavage of fenofibrate (100 mg/kg/day) in the form of Daunlip suspended in phosphate-buffered saline (PBS), for a period of 14 consecutive days. The treatment began the same day of the infection until the end of the experiment.…”