Canonical PI3Kγ signaling in myeloid cells restricts Trypanosoma cruzi infection and dampens chagasic myocarditis
| Autor: | Thiago M. Cunha, Lucas Esteves Cardozo, Florêncio Figueiredo, Konstantina Lyroni, Emilio Hirsch, F. N. Gava, João Santana da Silva, Edecio Cunha-Neto, Renata Sesti-Costa, Christophe Chevillard, Carla D. Lopes, Maria R. C. da Silva, Marcela Davoli-Ferreira, Christos Tsatsanis, José C. Alves-Filho, Fernando Q. Cunha, Fabrício C. Dias, Helder I. Nakaya, Monique Andrade Baron, Amanda Farage Frade, Tiago Medina, Grace K. Silva |
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| Přispěvatelé: | University of Minho [Braga], Universidade do Porto = University of Porto, School of Medicine of Ribeirão Preto (FMRP), Universidade de São Paulo = University of São Paulo (USP), Heart Institute (InCor), Universidade de São Paulo = University of São Paulo (USP)-Faculdade de Medicina FMUSP, Yerkes National Primate Research Center [Lawrenceville, GA], Emory University [Atlanta, GA], Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Genetics, Biology and Biochemistry, Université de Turin, Instituto de Engenharia de Sistemas e Computadores Investigação e Desenvolvimento em Lisboa (INESC-ID), Instituto Superior Técnico, Universidade Técnica de Lisboa (IST)-Instituto de Engenharia de Sistemas e Computadores (INESC), ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), University of Porto, School of Medicine of Ribeirão Preto ( FMRP ), University of São Paulo ( USP ), Heart Institute ( InCor ), Universidade de São Paulo ( USP ) -Faculdade de Medicina FMUSP, Yerkes National Primate Research Centre, Theories and Approaches of Genomic Complexity ( TAGC ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Technologies avancées pour le génôme et la clinique ( TAGC ), Instituto de Engenharia de Sistemas e Computadores Investigação e Desenvolvimento em Lisboa ( INESC-ID ), Instituto Superior Técnico, Universidade Técnica de Lisboa ( IST ) -Instituto de Engenharia de Sistemas e Computadores ( INESC ), Universidade do Porto, University of São Paulo (USP), Universidade de São Paulo (USP)-Faculdade de Medicina FMUSP, Faculdade de Medicina FMUSP-Universidade de São Paulo (USP) |
| Rok vydání: | 2018 |
| Předmět: |
Chagas Cardiomyopathy
Male 0301 basic medicine Chagas disease Heart disease Biopsy [SDV]Life Sciences [q-bio] Cardiomyopathy General Physics and Astronomy 030204 cardiovascular system & hematology Inbred C57BL Mice 0302 clinical medicine [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology Protozoan infections Class Ib Phosphatidylinositol 3-Kinase Myeloid Cells lcsh:Science ComputingMilieux_MISCELLANEOUS Phosphoinositide-3 Kinase Inhibitors Mice Knockout Multidisciplinary Heart Middle Aged Canonical Up-Regulation 3. Good health [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology Female Signal transduction Signal Transduction Adult [ SDV.MP.PAR ] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology Myocarditis Knockout Trypanosoma cruzi Science [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Biology Article General Biochemistry Genetics and Molecular Biology Cell Line 03 medical and health sciences Downregulation and upregulation Quinoxalines Protozoan infection parasitic diseases medicine Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry Molecular Biology [ SDV ] Life Sciences [q-bio] Animal Myocardium [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Molecular mechanisms General Chemistry Disease Models Animal Mice Inbred C57BL Thiazolidinediones medicine.disease biology.organism_classification 030104 developmental biology Disease Models Immunology MIOCARDIOPATIAS lcsh:Q |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-14 (2018) Nature Communications Nature Communications, Nature Publishing Group, 2018, 9 (1), ⟨10.1038/s41467-018-03986-3⟩ Nature Communications, Nature Publishing Group, 2018, 9 (1), 〈10.1038/s41467-018-03986-3〉 Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 2041-1723 |
| Popis: | Chagas disease is caused by infection with the protozoan Trypanosoma cruzi (T. cruzi) and is an important cause of severe inflammatory heart disease. However, the mechanisms driving Chagas disease cardiomyopathy have not been completely elucidated. Here, we show that the canonical PI3Kγ pathway is upregulated in both human chagasic hearts and hearts of acutely infected mice. PI3Kγ-deficient mice and mutant mice carrying catalytically inactive PI3Kγ are more susceptible to T. cruzi infection. The canonical PI3Kγ signaling in myeloid cells is essential to restrict T. cruzi heart parasitism and ultimately to avoid myocarditis, heart damage, and death of mice. Furthermore, high PIK3CG expression correlates with low parasitism in human Chagas’ hearts. In conclusion, these results indicate an essential role of the canonical PI3Kγ signaling pathway in the control of T. cruzi infection, providing further insight into the molecular mechanisms involved in the pathophysiology of chagasic heart disease. Trypanosoma cruzi infection causes Chagas disease, but mechanisms underlying pathogenesis are unclear. Here, Silva et al. show that canonical PI3Kγ signaling in myeloid cells restricts T. cruzi infection in mice and that high PIK3CG expression correlates with low parasite levels in human Chagas’ hearts. |
| Databáze: | OpenAIRE |
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