title: Aspirin modulates innate inflammatory response and inhibits the entry of Trypanosoma cruzi in mouse peritoneal macrophages.
abstract: The intracellular protozoan parasite Trypanosoma cruzi causes Chagas disease, a serious disorder that affects millions of people in Latin America. Cell invasion by T. cruzi and its intracellular replication are essential to the parasite's life cycle and for the development of Chagas disease. Here, we present evidence suggesting the involvement of the host's cyclooxygenase (COX) enzyme during T. cruzi invasion. Pharmacological antagonist for COX-1, aspirin (ASA), caused marked inhibition of T. cruzi infection when peritoneal macrophages were pretreated with ASA for 30 min at 37°C before inoculation. This inhibition was associated with increased production of IL-1β and nitric oxide (NO(∙)) by macrophages. The treatment of macrophages with either NOS inhibitors or prostaglandin E2 (PGE2) restored the invasive action of T. cruzi in macrophages previously treated with ASA. Lipoxin ALX-receptor antagonist Boc2 reversed the inhibitory effect of ASA on trypomastigote invasion. Our results indicate that PGE2, NO(∙), and lipoxins are involved in the regulation of anti-T. cruzi activity by macrophages, providing a better understanding of the role of prostaglandins in innate inflammatory response to T. cruzi infection as well as adding a new perspective to specific immune interventions.
authors.affiliation: Laboratório de Imunopatologia Experimental, Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970 Londrina, PR, Brazil.
authors.forename: Aparecida Donizette
authors.initials: AD
authors.lastname: Malvezi
authors.affiliation: Laboratório de Imunopatologia Experimental, Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970 Londrina, PR, Brazil.
authors.forename: Rosiane Valeriano
authors.initials: RV
authors.lastname: da Silva
authors.affiliation: Laboratório de Imunopatologia Experimental, Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970 Londrina, PR, Brazil.
authors.forename: Carolina
authors.initials: C
authors.lastname: Panis
authors.affiliation: Laboratório de Biologia Molecular de Microrganismos, Departamento de Microbiologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970 Londrina, PR, Brazil.
authors.forename: Lucy Megumi
authors.initials: LM
authors.lastname: Yamauchi
authors.affiliation: Laboratório de Imunopatologia Experimental, Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970 Londrina, PR, Brazil.
authors.forename: Maria Isabel
authors.identifier: 0000-0002-9102-2787
authors.initials: MI
authors.lastname: Lovo-Martins
authors.affiliation: Laboratório de Imunopatologia Experimental, Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970 Londrina, PR, Brazil.
authors.forename: Nagela Ghabdan
authors.initials: NG
authors.lastname: Zanluqui
authors.affiliation: Laboratório de Imunopatologia Experimental, Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970 Londrina, PR, Brazil.
authors.forename: Vera Lúcia Hideko
authors.initials: VL
authors.lastname: Tatakihara
authors.affiliation: Instituto Israelita de Ensino e Pesquisa Albert Einstein, 056510-901 São Paulo, SP, Brazil.
authors.forename: Luiz Vicente
authors.initials: LV
authors.lastname: Rizzo
authors.affiliation: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970 Londrina, PR, Brazil.
authors.forename: Waldiceu A
authors.initials: WA
authors.lastname: Verri
authors.affiliation: Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970 Londrina, PR, Brazil.
authors.forename: Marli Cardoso
authors.initials: MC
authors.lastname: Martins-Pinge
authors.affiliation: Laboratório de Biologia Molecular de Microrganismos, Departamento de Microbiologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970 Londrina, PR, Brazil.
authors.forename: Sueli Fumie
authors.identifier: 0000-0003-1183-146X
authors.initials: SF
authors.lastname: Yamada-Ogatta
authors.affiliation: Laboratório de Imunopatologia Experimental, Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970 Londrina, PR, Brazil.
authors.forename: Phileno
authors.initials: P
authors.lastname: Pinge-Filho
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000469:parasitology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D052247:Nitric Oxide Synthase Type II; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000472:pathogenicity*
chemical_list: D053583:Interleukin-1beta; D052247:Nitric Oxide Synthase Type II; D001241:Aspirin