CD39 expression by regulatory T cells participates in CD8+ T cell suppression during experimental Trypanosoma cruzi infection
Date
2024-04-29Author
Araujo Furlan, Cintia L.
Santiago, Boccardo
Rodriguez, Constanza
Mary, Verónica S.
Gimenez, Camila M. S.
Robson, Simon C.
Gruppi, Adriana
Montes, Carolina L.
Acosta Rodríguez, Eva V.
ORCID
https://orcid.org/0009-0003-1527-870Xhttps://orcid.org/0000-0001-9578-495X
https://orcid.org/0009-0003-1623-3511
https://orcid.org/0000-0001-5871-2391
Metadata
Show full item recordAbstract
An imbalance between suppressor and effector immune responses may preclude cure in
chronic parasitic diseases. In the case of Trypanosoma cruzi infection, specialized regulatory
Foxp3+ T (Treg) cells suppress protective type-1 effector responses. Herein, we investigated
the kinetics and underlying mechanisms behind the regulation of protective parasitespecific
CD8+ T cell immunity during acute T. cruzi infection. Using the DEREG mouse
model, we found that Treg cells play a role during the initial stages after T. cruzi infection,
restraining the magnitude of CD8+ T cell responses and parasite control. Early Treg cell
depletion increased the frequencies of polyfunctional short-lived, effector T cell subsets,
without affecting memory precursor cell formation or the expression of activation, exhaustion
and functional markers. In addition, Treg cell depletion during early infection minimally
affected the antigen-presenting cell response but it boosted CD4+ T cell responses before
the development of anti-parasite effector CD8+ T cell immunity. Crucially, the absence of
CD39 expression on Treg cells significantly bolstered effector parasite-specific CD8+ T cell
responses, preventing increased parasite replication in T. cruzi infected mice adoptively
transferred with Treg cells. Our work underscores the crucial role of Treg cells in regulating
protective anti-parasite immunity and provides evidence that CD39 expression by Treg cells
represents a key immunomodulatory mechanism in this infection model.
xmlui.dri2xhtml.METS-1.0.item-citation
Araujo Furlan CL, Boccardo S, Rodriguez C, Mary VS, Gimenez CMS, Robson SC, et al. (2024) CD39 expression by regulatory T cells participates in CD8+ T cell suppression during experimental Trypanosoma cruzi infection. PLoS Pathog 20(4): e1012191. https://doi.org/10.1371/ journal.ppat.1012191
Other links
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1012191https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11081507/
Collections
The following license files are associated with this item: