Dual role of monocyte‐derived dendritic cells in <i>Trypanosoma cruzi</i> infection

Poncini, Carolina Verónica; González-Cappa, Stella Maris

doi:10.1002/eji.201646830

Cited by 15 publications

(28 citation statements)

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“…Mice received a single intraperitoneal injection of 5′Fluorouracil (5FU, 50 mg/kg), a dose proven to specifically deplete MDSC without affecting other splenic cell populations (Vincent et al, 2010 ; Poncini and González-Cappa, 2017 ), at day 4 post-inoculation with S. aureus . MDSC depletion was confirmed by flow cytometry analysis after staining spleen cells with antibodies against CD11b, Gr-1, Ly6C, and Ly6G.…”

Section: Methodsmentioning

confidence: 99%

TNFR1 Signaling Contributes to T Cell Anergy During Staphylococcus aureus Sepsis

Ledo

González

Poncini

et al. 2018

Front. Cell. Infect. Microbiol.

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Early research on sepsis has focused on the initial hyper-inflammatory, cytokine mediated phase of the disorder whereas the events that govern the concomitant and subsequent anti-inflammatory compensatory response are not completely understood. In this context, the putative participation of TNFR1-mediated signaling in the immunosuppressive phase of Staphylococcus aureus sepsis has not been elucidated. The aim of this study was to determine the role of TNFR1 in directing the immune dysfunction during S. aureus sepsis and the potential contribution of MDSC to this process. Using a model of sepsis of peritoneal origin and tnfr1−/− mice, we demonstrated that during staphylococcal sepsis CD4+ T cell anergy is significantly dependent on TNFR1 expression and that signaling through this receptor has an impact on bacterial clearance in the spleen. MDSC played a major role in the generation of anergic CD4+ T cells and their accumulation in the spleen during S. aureus sepsis correlated with IL-6 induction. Although TNFR1 signaling was not required for MDSC accumulation and expansion in the spleen, it determined the in vivo expression of Arginase 1 and iNOS, enzymes known to participate in the suppressive function of this population. Moreover, our data indicate that TNFR1-mediated IL-10 production may modulate MDSC function during staphylococcal sepsis. Taken together these results indicate that TNFR1 plays a critical role on T cell dysfunction during S. aureus sepsis by regulating immunomodulatory mediators in MDSC. The role of TNFR1-mediated signaling during the immunosuppressive phase of staphylococcal sepsis should be considered when designing novel alternative therapeutic approaches.

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Section: Methodsmentioning

confidence: 99%

TNFR1 Signaling Contributes to T Cell Anergy During Staphylococcus aureus Sepsis

Ledo

González

Poncini

et al. 2018

Front. Cell. Infect. Microbiol.

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“…In addition, T. cruzi induces a DC death marker called PDL-1 that inhibits the production of proinflammatory cytokines such as IL-12, TNF- α , and IL-6 and stimulates the synthesis of anti-inflammatory cytokines such as IL-10 and TGF- β targeting a tolerogenic profile where there is less activation of T. cruzi -specific T lymphocytes [6, 25, 28, 37, 38]. These immunomodulations by the parasite can vary depending on the T. cruzi strain and how they interact with these cells, highlighting the key role of DCs in the development of clinical forms of the disease [6, 7, 37, 39–43]. Although many studies have elucidated the mechanisms by which T. cruzi modulates DCs, the interaction of these cells with Mexican strains has not yet been properly investigated.…”

Section: Introductionmentioning

confidence: 99%

Trypanosoma cruziMexican Strains Differentially Modulate Surface Markers and Cytokine Production in Bone Marrow-Derived Dendritic Cells from C57BL/6 and BALB/c Mice

Barbosa

Costa

Desidério

et al. 2019

Mediators of Inflammation

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Dendritic cells (DCs) are a type of antigen-presenting cells that play an important role in the immune response against Trypanosoma cruzi, the causative agent of Chagas disease. In vitro and in vivo studies have shown that the modulation of these cells by this parasite can directly affect the innate and acquired immune response of the host in order to facilitate its biological cycle and the spreading of the species. Many studies show the mechanisms by which T. cruzi modulates DCs, but the interaction of these cells with the Mexican strains of T. cruzi such as Ninoa and INC5 has not yet been properly investigated. Here, we evaluated whether Ninoa and INC5 strains evaded the immunity of their hosts by modulating the biology and function of murine DCs. The CL-Brener strain was used as the reference strain. Herein, it was demonstrated that Ninoa was more infective toward bone marrow-derived dendritic cells (BMDCs) than INC5 and CL-Brener strains in both BMDCs of BALB/c and C57BL/6 mice. Mexican strains of T. cruzi induced different cytokine patterns. In BMDCs obtained from BALB/c mice, Ninoa strain led to the reduction in IL-6 and increased IL-10 production, while in C57BL/6 mice Ninoa strain considerably increased the productions of TNF-α and IL-10. Also, Ninoa and INC5 differentially modulated BMDC expressions of MHC-II, TLR2, and TLR4 in both BALB/c and C57BL/6 mice compared to Brazilian strain CL-Brener. These results indicate that T. cruzi Mexican strains differentially infect and modulate MHC-II, toll-like receptors, and cytokine production in DCs obtained from C57BL/6 and BALB/c mice, suggesting that these strains have developed particular modulatory strategies to disrupt DCs and, consequently, the host immune responses.

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“…Unpublished results from our group demonstrate that the infection with mTp displays reduced cell infiltrate and response at the site of infection (Gutierrez, manuscript under redaction) in comparison with the response described for bTp (Poncini and González-Cappa, 2017). Here, we studied functional properties of BMDCs and XS106 cells stimulated with mTp or bTp in an MLR and found that mTp improved the capacity to induce lymphoproliferation in both cells.…”

Section: Discussionmentioning

confidence: 78%

“…The fact that the parasite successfully infects the mammalian host via different portals of entry and by different infective stages highlights the importance the model of infection acquires during experimentation. As a result, a detailed characterization of the interaction of the parasite with cells involved in the first line of defense during primoinfection was needed (Poncini and González-Cappa, 2017).…”

Section: Introductionmentioning

confidence: 99%

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

Gutierrez

Lammel

Ramirez

et al. 2020

Front. Cell. Infect. Microbiol.

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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.

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Dual role of monocyte‐derived dendritic cells in Trypanosoma cruzi infection

Cited by 15 publications

References 50 publications

TNFR1 Signaling Contributes to T Cell Anergy During Staphylococcus aureus Sepsis

TNFR1 Signaling Contributes to T Cell Anergy During Staphylococcus aureus Sepsis

Trypanosoma cruziMexican Strains Differentially Modulate Surface Markers and Cytokine Production in Bone Marrow-Derived Dendritic Cells from C57BL/6 and BALB/c Mice

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

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