1. Altered purinergic P2X7 and A 2B receptors signaling limits macrophage-mediated host defense in schistosomiasis.
- Author
-
Thorstenberg ML, Martins MDA, Oliveira NF, Monteiro MMLV, Santos GRC, Pereira HMG, Savio LEB, Coutinho-Silva R, and Silva CLM
- Subjects
- Animals, Mice, Schistosomiasis immunology, Schistosoma mansoni immunology, Leishmania immunology, Adenosine Triphosphate metabolism, Receptors, Purinergic P2X7 metabolism, Macrophages immunology, Macrophages metabolism, Signal Transduction, Mice, Inbred C57BL, Phagocytosis
- Abstract
Background: The occurrence of co-infections during schistosomiasis, a neglected tropical disease, with other parasites have been reported suggesting an impaired host immune defense. Macrophage purinergic P2X7 receptor (P2X7R) plays an important role against intracellular pathogens. Therefore, we investigated the P2X7R-mediated phagocytosis and killing capacity of Leishmania amazonensis by macrophages during schistosomiasis in vitro and in vivo., Methods: Swiss and C57BL/6 (Wild type) and P2X7R
-/- were randomized in two groups: control (uninfected) and Schistosoma mansoni-infected. Alternatively, control Swiss and S. mansoni-infected mice were also infected with L. amazonensis., Results: The pre-treatment of control macrophages with the P2X7R antagonist (A74003) or TGF-β reduced the phagocytosis index, mimicking the phenotype of cells from S. mansoni-infected mice and P2X7R-/- mice. Apyrase also reduced the phagocytosis index in the control group corroborating the role of ATP to macrophage activation. Moreover, l-arginine-nitric oxide pathway was compromised during schistosomiasis, which could explain the reduced killing capacity in response to ATP in vitro and in vivo. We found an increased extracellular nucleotide (ATP, ADP and AMP) hydrolysis along with an increased frequency of F4/80+ CD39+ macrophages from the S. mansoni-infected group. Moreover, the content of adenosine in the cell supernatant was higher in the S. mansoni-infected group in relation to controls. Schistosomiasis also increased the expression of macrophage adenosine A2B R. In good accordance, both ADA and the selective A2B R antagonist restored the phagocytosis index of macrophages from S. mansoni-infected group., Conclusions: Altogether, the altered P2X7R and A2B R signaling limits the role of macrophages to host defense against L. amazonensis during schistosomiasis, potentially contributing to the pathophysiology and clinically relevant co-infections., Competing Interests: Declaration of competing interest none., (© 2024 The Authors. Published by Elsevier B.V. on behalf of Chang Gung University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).) more...- Published
- 2024
- Full Text
- View/download PDF