Arginase I, Polyamine and Prostaglandin E2 Pathways Suppress the Inflammatory Response and Contribute to Diffuse Cutaneous Leishmaniasis
2015
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.
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