Open AccessCyclooxygenase‐derived mediators regulate the immunological control of Strongyloides venezuelensis infection
Author(s) -
Machado Eleuza R.,
Carlos Daniela,
Lourenço Elaine V.,
Souza Glória E.P.,
Sorgi Carlos A.,
Silva Érika V.,
Ueta Marlene T.,
Ramos Simone G.,
Aronoff David M.,
Faccioli Lúcia H.
Publication year - 2010
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1111/j.1574-695x.2010.00656.x
Subject(s) - cyclooxygenase , strongyloides , bronchoalveolar lavage , immunology , biology , prostaglandin e2 , eicosanoid , pharmacology , lung , medicine , endocrinology , arachidonic acid , helminths , enzyme , biochemistry
Abstract The aim of this study was to define the immunoregulatory role of prostaglandins in a mouse model of Strongyloides venezuelensis infection. Strongyloides venezuelensis induced an increase of eosinophils and mononuclear cells in the blood, peritoneal cavity fluid, and bronchoalveolar lavage fluid. Treatment with the dual cyclooxygenase (COX‐1/‐2) inhibitors indomethacin and ibuprofen, and the COX‐2‐selective inhibitor celecoxib partially blocked these cellular responses and was associated with enhanced numbers of infective larvae in the lung and adult worms in the duodenum. However, the drugs did not interfere with worm fertility. Cyclooxygenase inhibitors also inhibited the production of the T‐helper type 2 (Th2) mediators IL‐5, IgG1, and IgE, while indomethacin alone also inhibited IL‐4, IL‐10, and IgG2a. Cyclooxygenase inhibitors tended to enhance the Th1 mediators IL‐12 and IFN‐γ. This shift away from Th2 immunity in cyclooxygenase inhibitor‐treated mice correlated with reduced prostaglandin E 2 (PGE 2 ) production in infected duodenal tissue. As PGE 2 is a well‐characterized driver of Th2 immunity, we speculate that reduced production of this lipid might be involved in the shift toward a Th1 phenotype, favoring parasitism by S. venezuelensis . These findings provide new evidence that cyclooxygenase‐derived lipids play a role in regulating host defenses against Strongyloides , and support the exploration of eicosanoid signaling for identifying novel preventive and therapeutic modalities against these infections.