Role of formyl peptide receptor 2 (FPR2) in modulating immune response and heart inflammation in an experimental model of acute and chronic Chagas disease

• Published in: Cellular immunology Vol. 369; p. 104427
• Main Authors: das Dores Pereira, Rafaela, Rabelo, Rayane Aparecida Nonato, Leite, Paulo Gaio, Cramer, Allysson, Botelho, Ana Flávia Machado, Cruz, Jader Santos, Régis, Wiliam César Bento, Perretti, Mauro, Teixeira, Mauro Martins, Machado, Fabiana Simão
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-11-2021
• Subjects: Animals; Chagas Cardiomyopathy; Chagas Cardiomyopathy - complications; Chagas Cardiomyopathy - immunology; Disease Models, Animal; Female; Formyl Peptide Receptor; Immunorregulation; Innate and acquired immune responses; Macrophages - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocarditis - immunology; Receptors, Formyl Peptide - immunology; T-Lymphocytes - immunology; Trypanossoma cruzi; Immunorregulation; Innate and acquired immune responses; Chagas Cardiomyopathy; Formyl Peptide Receptor; Trypanossoma cruzi
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2021.104427

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•Macrophages trypanocidal activity is regulated by FPR2.•FPR2 regulates the generation/expansion of immune cells during T. cruzi infection.•FPR2 is critical to control the development of myocarditis during T. cruzi infection.•Deficiency of FPR2 is associated with worse heart dysfunction during infection.•FPR2 is a potential new therapeutic target for Chagas disease treatment.
Chagas disease is an important disease of the heart. Lipoxins have important regulatory functions in host immune response (IR). Herein, we examined whether the receptor for lipoxin A4, the formyl peptide receptor (FPR) 2, had an effect on Trypanosoma cruzi infection. In vitro, FPR2 deficiency or inhibition improved the activity of macrophages against T. cruzi. In vivo, during the acute phase, the absence of FPR2 reduced parasitemia and increased type 2 macrophages, type 2 neutrophils, and IL-10-producing dendritic cells. Moreover, the acquired IR was characterized by greater proportions of Th1/Th2/Treg, and IFNγ-producing CD8+T cells, and reductions in Th17 and IL-17-producing CD8+T cells. However, during the chronic phase, FPR2 deficient mice presented and increased inflammatory profile regarding innate and acquired IR cells (Th1/IFN-γ-producing CD8+T cells). Notably, FPR2 deficiency resulted in increased myocarditis and impaired heart function. Collectively, our data suggested that FPR2 is important for the orchestration of IR and prevention of severe T. cruzi-induced disease.