Inflammatory responses are terminated by the clearance of dead cells, a process termed efferocytosis. A consequence of efferocytosis is the synthesis of the antiinflammatory mediators TGF-β, PGE, and IL-10; however, the efferocytosis of infected cells favors Th17 responses by eliciting the synthesis of TGF-β, IL-6, and IL-23. Recently, we showed that the efferocytosis of apoptotic -infected macrophages by dendritic cells triggers PGE production in addition to pro-Th17 cytokine expression. We therefore examined the role of PGE during Th17 differentiation and intestinal pathology. The efferocytosis of apoptotic -infected cells by dendritic cells promoted high levels of PGE, which impaired IL-1R expression via the EP4-PKA pathway in T cells and consequently inhibited Th17 differentiation. The outcome of murine intestinal infection was dependent on the EP4 receptor. Infected mice treated with EP4 antagonist showed enhanced intestinal defense against compared with infected mice treated with vehicle control. Those results suggest that EP4 signaling during infectious colitis could be targeted as a way to enhance Th17 immunity and host defense.

Efferocytosis, or clearance of apoptotic cells (ACs), by dendritic cells (DCs) leads to immune response suppression and tolerance to self-antigens. However, efferocytosis of infected apoptotic cells (IACs) leads to the production of a mixed pro- and anti-inflammatory cytokine milieu. We examined the DC phenotype and ability to migrate after phagocytosis of ACs or IACs and observed higher levels of CD86 and CCR7 expression in DCs, as well as enhanced migration capacity following efferocytosis of IACs. Interestingly, higher levels of interleukin-1β, interleukin-10 and prostaglandin E (PGE ) were also produced in this context. Blockage of IAC recognition led to an impaired maturation profile and PGE production, which may have contributed to reduced CD86 and CCR7 expression and migration capacity. These data contribute to the understanding of how efferocytosis of sterile or infected cells may regulate the adaptive immune response, although the precise role of PGE in this process requires further investigation.

A B S T R A C TThis work investigates the effect of a soy-based probiotic drink (Enterococcus faecium CRL 183 and Bifidobacterium longum ATCC 15707) on the fecal microbiota composition, body weight and inflammatory parameters in diet-induced obese mice. The probiotic group had a lower body weight until 9th week of the study, reduced area and diameter of adipocytes, and showed a significant increase of IL-6 and IL-10 compared to the obesite non-treated group. The intake of a high-fat diet results in an increase of Lactobacillus spp. while the probiotic drink positively modulates the intestinal microbiota by maintaining the population of microorganisms belonging to the phylum Bacteroidetes and increases Bifidobacterium spp. Our study finds that the regular intake of this probiotic drink is able to reduce body weight gain and the size of adipocytes while modulating the fecal microbiota and the immune profile of animals, therefore acting in a beneficial manner in the control of obesity.

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