Cyclooxygenase-derived mediators regulate the immunological control of Strongyloides venezuelensis infection


Autoria(s): MACHADO, Eleuza R.; CARLOS, Daniela; LOURENCO, Elaine V.; SOUZA, Gloria E. P.; SORGI, Carlos A.; SILVA, Erika V.; UETA, Marlene T.; RAMOS, Simone G.; ARONOFF, David M.; FACCIOLI, Lucia H.
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

19/10/2012

19/10/2012

2010

Resumo

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-gamma. 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.

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)

Coordenacao de Aperfeicoamento de Pessoal de Ensino Superior (CAPES)

Identificador

FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY, v.59, n.1, p.18-32, 2010

0928-8244

http://producao.usp.br/handle/BDPI/20329

10.1111/j.1574-695X.2010.00656.x

http://dx.doi.org/10.1111/j.1574-695X.2010.00656.x

Idioma(s)

eng

Publicador

WILEY-BLACKWELL

Relação

Fems Immunology and Medical Microbiology

Direitos

restrictedAccess

Copyright WILEY-BLACKWELL

Palavras-Chave #Immune response #Strongyloides venezuelensis #PGE(2) #eosinophils #cytokine #antibody #NONSTEROIDAL ANTIINFLAMMATORY DRUGS #PROSTAGLANDIN D-2 RECEPTOR #CUTTING EDGE #IN-VITRO #PROTECTIVE IMMUNITY #SCHISTOSOMA-MANSONI #KAPPA-B #MICE #CELECOXIB #STERCORALIS #Immunology #Infectious Diseases #Microbiology
Tipo

article

original article

publishedVersion