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Title: Arginase I, Polyamine and Prostaglandin E2 Pathways Suppress the Inflammatory Response and Contribute to Diffuse Cutaneous Leishmaniasis
Authors: França-Costa, Jaqueline ×
Van Weyenbergh, Johan
Boaventura, Viviane S
Luz, Nívea F
Malta-Santos, Hayna
Oliveira, Murilo Cezar Souza
Santos de Campos, Daniela Conceição
Saldanha, Ana Cristina
Dos-Santos, Washington L C
Bozza, Patrícia T
Barral-Netto, Manoel
Barral, Aldina
Costa, Jackson M
Borges, Valeria M #
Issue Date: Feb-2015
Series Title: The Journal of infectious diseases vol:211 issue:3 pages:426-435
Article number: jiu455
Abstract: Diffuse cutaneous leishmaniasis (DCL) is a rare clinical manifestation of tegumentary leishmaniasis. The molecular mechanisms underlying DCL pathogenesis remain unclear, and there is no efficient treatment available. This study investigated the systemic and in situ expression of the inflammatory response that might contribute to suppression in DCL. The plasma levels of arginase, ODC, TGF-β and PGE2 were higher in DCL patients, than those from LCL patients or endemic control. In situ transcriptomic analyses reinforced the association between arginase expression and enzymes involved in prostaglandin and polyamine synthesis. Immunohistochemistry confirmed that arginase I, ODC and cyclooxygenase2 expression was higher in DCL than in LCL lesions. Inhibition of arginase or ODC abrogates L. amazonensis replication in infected human macrophages. Our data implicate arginase I, ODC, PGE2 and TGF-β in the failure to mount an efficient immune response and suggest perspectives in the development of new strategies for therapeutic intervention for DCL patients.
URI: 
ISSN: 0022-1899
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Clinical and Epidemiological Virology (Rega Institute)
× corresponding author
# (joint) last author

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