AUTHOR=Lonien Sandra C. H. , Malvezi Aparecida D. , Suzukawa Helena T. , Yamauchi Lucy M. , Yamada-Ogatta Sueli F. , Rizzo Luiz V. , Bordignon Juliano , Pinge-Filho Phileno 

TITLE=Response to Trypanosoma cruzi by Human Blood Cells Enriched with Dentritic Cells Is Controlled by Cyclooxygenase-2 Pathway

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 8 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.02020

DOI=10.3389/fmicb.2017.02020

ISSN=1664-302X

ABSTRACT=About 6 million to 7 million people worldwide, mostly in Latin America, are estimated to be infected with Trypansosoma cruzi, the parasite that causes Chagas disease. It seems that T. cruzi virulent strains take advantage of susceptible dendritic cells (DCs) to overcome host immune response and successfully install the infection. Although DCs are characterized by enormous functional diversity, it has not been analyzed how DCs interact with T. cruzi via a cyclooxygenase (COX) and cyclic adenosine monophosphate (cAMP) dependent pathway. We have previously described that nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the invasion of T. cruzi into rat cardiac cells and promote differential modulation of the inflammatory response. By exploiting this mechanism, dendritic cells (DCs) from monocytes isolated by adherence from peripheral blood mononuclear cells (PBMCs) were used as our model. Our results showed that the treatment of MDDCs with celecoxib (CEL), a cyclooxygenase-2 selective inhibitor or SQ 22,536, adenilate cyclase inhibitor, significantly caused marked inhibition of T. cruzi infection. This inhibition was not observed when the cells were treated only with aspirin (ASA, a non-selective COX-1 and COX-2 inhibitor) and was independent of nitric oxide production.  The expression of co-stimulatory molecules CD80 and CD86 were similar on MDDCs treated or not with both COX-inhibitors. The infection did not stimulated the release of TNF-α but increased IL-1β, IL-6, IL-8 and IL-10 production by infected MDDCs. Treatment with ASA or CEL did not affect TNF-α, IL-6, IL-8, IL-10 and NO production by infected MDDCs, but increased IL-1β production by them. Our results reinforce the idea that the COX-2 pathway plays a fundamental role in the process of T. cruzi invasion and provide a better understanding of the influence of COX-interfering therapies on the innate inflammatory response to T. cruzi infection and may represent a very pertinent target for new therapeutic treatments of Chagas disease.