Altered purinergic P2X7 and A2B receptors signaling limits macrophage-mediated host defense in schistosomiasis
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 inv...
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Elsevier
2024-12-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2319417024000167 |
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| author | Maria Luiza Thorstenberg Monique Daiane Andrade Martins Nathália Ferreira Oliveira Matheus Macedo L.V. Monteiro Gustavo R.C. Santos Henrique M. Gualberto Pereira Luiz Eduardo Baggio Savio Robson Coutinho-Silva Claudia Lucia Martins Silva |
| author_facet | Maria Luiza Thorstenberg Monique Daiane Andrade Martins Nathália Ferreira Oliveira Matheus Macedo L.V. Monteiro Gustavo R.C. Santos Henrique M. Gualberto Pereira Luiz Eduardo Baggio Savio Robson Coutinho-Silva Claudia Lucia Martins Silva |
| author_sort | Maria Luiza Thorstenberg |
| collection | DOAJ |
| description | 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 A2BR. In good accordance, both ADA and the selective A2BR antagonist restored the phagocytosis index of macrophages from S. mansoni-infected group. Conclusions: Altogether, the altered P2X7R and A2BR signaling limits the role of macrophages to host defense against L. amazonensis during schistosomiasis, potentially contributing to the pathophysiology and clinically relevant co-infections. |
| format | Article |
| id | doaj-art-b5876f95cef54269b28b05ae9f4672ec |
| institution | OA Journals |
| issn | 2319-4170 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
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| spelling | doaj-art-b5876f95cef54269b28b05ae9f4672ec2025-08-20T02:37:51ZengElsevierBiomedical Journal2319-41702024-12-0147610071310.1016/j.bj.2024.100713Altered purinergic P2X7 and A2B receptors signaling limits macrophage-mediated host defense in schistosomiasisMaria Luiza Thorstenberg0Monique Daiane Andrade Martins1Nathália Ferreira Oliveira2Matheus Macedo L.V. Monteiro3Gustavo R.C. Santos4Henrique M. Gualberto Pereira5Luiz Eduardo Baggio Savio6Robson Coutinho-Silva7Claudia Lucia Martins Silva8Laboratory of Biochemical and Molecular Pharmacology, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, BrazilLaboratory of Immunophysiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, BrazilLaboratory of Biochemical and Molecular Pharmacology, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, BrazilLaboratory of Biochemical and Molecular Pharmacology, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, BrazilBrazilian Doping Control Laboratory (LBCD – LADETEC / IQ), Universidade Federal do Rio de Janeiro, BrazilBrazilian Doping Control Laboratory (LBCD – LADETEC / IQ), Universidade Federal do Rio de Janeiro, BrazilLaboratory of Immunophysiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, BrazilLaboratory of Immunophysiology, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, BrazilLaboratory of Biochemical and Molecular Pharmacology, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Brazil; Corresponding author. Laboratory of Biochemical and Molecular Pharmacology, ICB, UFRJ, room J-17, Av. Carlos Chagas Filho, 373, CCS, Rio de Janeiro, Brazil.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 A2BR. In good accordance, both ADA and the selective A2BR antagonist restored the phagocytosis index of macrophages from S. mansoni-infected group. Conclusions: Altogether, the altered P2X7R and A2BR signaling limits the role of macrophages to host defense against L. amazonensis during schistosomiasis, potentially contributing to the pathophysiology and clinically relevant co-infections.http://www.sciencedirect.com/science/article/pii/S2319417024000167MacrophagesSchistosomiasisHost defenseAdenosine receptorP2X7 receptorLeishmaniasis |
| spellingShingle | Maria Luiza Thorstenberg Monique Daiane Andrade Martins Nathália Ferreira Oliveira Matheus Macedo L.V. Monteiro Gustavo R.C. Santos Henrique M. Gualberto Pereira Luiz Eduardo Baggio Savio Robson Coutinho-Silva Claudia Lucia Martins Silva Altered purinergic P2X7 and A2B receptors signaling limits macrophage-mediated host defense in schistosomiasis Biomedical Journal Macrophages Schistosomiasis Host defense Adenosine receptor P2X7 receptor Leishmaniasis |
| title | Altered purinergic P2X7 and A2B receptors signaling limits macrophage-mediated host defense in schistosomiasis |
| title_full | Altered purinergic P2X7 and A2B receptors signaling limits macrophage-mediated host defense in schistosomiasis |
| title_fullStr | Altered purinergic P2X7 and A2B receptors signaling limits macrophage-mediated host defense in schistosomiasis |
| title_full_unstemmed | Altered purinergic P2X7 and A2B receptors signaling limits macrophage-mediated host defense in schistosomiasis |
| title_short | Altered purinergic P2X7 and A2B receptors signaling limits macrophage-mediated host defense in schistosomiasis |
| title_sort | altered purinergic p2x7 and a2b receptors signaling limits macrophage mediated host defense in schistosomiasis |
| topic | Macrophages Schistosomiasis Host defense Adenosine receptor P2X7 receptor Leishmaniasis |
| url | http://www.sciencedirect.com/science/article/pii/S2319417024000167 |
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