Raíssa Fonseca, Rafael Moysés Salgado, Henrique Borges da Silva, Rogério Silva do Nascimento, Maria Regina D’Império-Lima, José Maria Alvarez
Abstract
Chagas disease is a neglected parasitic infection that affects around six to seven million people, mainly in Latin America. About 30-35% of infected people present chronic Chagas cardiomyopathy (CCC), which eventually leads to death. This condition is characterized by local parasite persistence and leukocyte infiltration. In a murine model of CCC, we observed that among infiltrating leukocytes, CD4+ and CD8+ T cells were in higher frequency in the heart of chronically infected mice, although elevated expression of the regulatory molecules programmed cell death protein 1 (PD1) and PDL1 suggested these cells could be inhibited. To investigate if PD1-PDL1 interaction in the heart of chronically infected mice negatively impacts on the local immune response, facilitating parasite persistence, and progression to CCC, we attempted to recover the local immune response by treating chronically infected mice with anti-PD1 and anti-PDL1-blocking antibodies together with irradiated Trypanosoma cruzi, which provides immune response boosting. Irradiated parasites promote expression of costimulatory molecules in dendritic cells and provide specific parasite antigen, which should aid T cell reactivation upon checkpoint blockade. Following treatment, there was an increased frequency of heart-infiltrating CD4+ and CD8+ T cells with an effector memory phenotype, an increased histopathology score and decreased heart rate, supporting our previous hypothesis of local immunosuppression induced by this pathway during CCC. In addition, blood parasitemia was reduced, which was associated with increased T. cruzi-specific immunoglobulin G 1 antibodies. However, no difference was observed in cytokine production or T. cruzi burden in the hearts of treated mice. Taken together, our results suggest PD1-PDL1 interaction protects the heart from excessive immune response.
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 May 2018.
All research outputs
#15,885,088
of 25,932,719 outputs
Outputs from Frontiers in immunology
#15,530
of 32,608 outputs
Outputs of similar age
#189,700
of 343,898 outputs
Outputs of similar age from Frontiers in immunology
#424
of 725 outputs
Altmetric has tracked 25,932,719 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 32,608 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.5. This one has gotten more attention than average, scoring higher than 51% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 343,898 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 43rd percentile – i.e., 43% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 725 others from the same source and published within six weeks on either side of this one. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.
