Cyclooxygenase-2 and prostaglandin E<inf>2</inf> signaling through prostaglandin receptor EP- 2 favor the development of myocarditis during acute trypanosoma cruzi infection

Inflammation plays an important role in the pathophysiology of Chagas disease, caused by Trypanosoma cruzi. Prostanoids are regulators of homeostasis and inflammation and are produced mainly by myeloid cells, being cyclooxygenases, COX-1 and COX-2, the key enzymes in their biosynthesis from arachidonic acid (AA). Here, we have investigated the expression of enzymes involved in AA metabolism during T. cruzi infection. Our results show an increase in the expression of several of these enzymes in acute T. cruzi infected heart. Interestingly, COX-2 was expressed by CD68+ myeloid heart-infiltrating cells. In addition, infiltrating myeloid CD11b+Ly6G- cells purified from infected heart tissue express COX-2 and produce prostaglandin E2 (PGE2) ex vivo. T. cruzi infections in COX-2 or PGE2- dependent prostaglandin receptor EP-2 deficient mice indicate that both, COX-2 and EP-2 signaling contribute significantly to the heart leukocyte infiltration and to the release of chemokines and inflammatory cytokines in the heart of T. cruzi infected mice. In conclusion, COX-2 plays a detrimental role in acute Chagas disease myocarditis and points to COX-2 as a potential target for immune intervention.This work was supported by (NG) grants from “Fondo de Investigaciones Sanitarias” (PS09/00538 and PI12/00289); “Universidad Autónoma de Madrid” and “Comunidad de Madrid” (CC08-UAM/SAL-4440/08); by (MF) grants from “Ministerio de Ciencia e Innovación” (SAF2010-17833); “Red de Investigación de Centros de Enfermedades Tropicales” (RICET RD12/0018/0004); European Union (HEALTH-FE-2008-22303, ChagasEpiNet); AECID Cooperation with Argentine (A/025417/09 and A/031735/10), Comunidad de Madrid (S-2010/BMD- 2332) and “Fundación Ramón Areces”. NAG was recipient of a ISCIII Ph.D. fellowship financed by the Spanish “Ministerio de Sanidad”. CCM and HC were recipients of contracts from SAF2010-17833 and PI060388, respectively.Peer Reviewe

Functional Seasonality of Free-Living and Particle-Associated Prokaryotic Communities in the Coastal Adriatic Sea

Marine snow is an important habitat for microbes, characterized by chemical and physical properties contrasting those of the ambient water. The higher nutrient concentrations in marine snow lead to compositional differences between the ambient water and the marine snow-associated prokaryotic community. Whether these compositional differences vary due to seasonal environmental changes, however, remains unclear. Thus, we investigated the seasonal patterns of the free-living and marine snow-associated microbial community composition and their functional potential in the northern Adriatic Sea. Our data revealed seasonal patterns in both, the freeliving and marine snow-associated prokaryotes. The two assemblages were more similar to each other in spring and fall than in winter and summer. The taxonomic distinctness resulted in a contrasting functional potential. Motility and adaptations to low temperature in winter and partly anaerobic metabolism in summer characterized the marine snow-associated prokaryotes. Free-living prokaryotes were enriched in genes indicative for functions related to phosphorus limitation in winter and in genes tentatively supplementing heterotrophic growth with proteorhodopsins and CO-oxidation in summer. Taken together, the results suggest a strong influence of environmental parameters on both free-living and marine snow-associated prokaryotic communities in spring and fall leading to higher similarity between the communities, while the marine snow habitat in winter and summer leads to a specific prokaryotic community in marine snow in these two seasons.Postprin