Distinctive role of efferocytosis in dendritic cell maturation and migration in sterile or infectious conditions

Abstract

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.

The immune response to secondary necrotic cells

“…Interestingly, the uptake of apoptotic micro particles by DCs induce an upregulation of CD80 and CD86 [ 90 ]. Efferocytosis of apoptotic cells, in contrast, has no effect on the expression of CD86 on DCs [ 91 ]. The specific effect of ingestion of secondary necrotic cells is unknown.…”

Intestinal host defense outcome is dictated by PGE 2 production during efferocytosis of infected cells

“…Generation of CM from Cocultures of BMDCs and IACs. BMDCs were differentiated with GM-CSF (PeproTech) for 7 d (12,13). RAW 264.7 cells were cultured with E. coli (ATCC 25922) (ratio 1:10) for 2 h to allow infection.…”

“…Then, the cells were washed with PBS to remove bacteria and cellular debris. RAW 264.7 infected cells were exposed to UVC radiation and maintained in a humidified 37°C 5% CO 2 incubator for 4 h, as previously described (12,13). BMDCs were treated with 10 μM of indomethacin or left untreated.…”

“…Innate recognition of apoptotic E. coli-infected cells leads to TGF-β, IL-6, and IL-23 production and favors Th17 cell differentiation (7). We previously showed that PGE 2 and IL-1β are also produced during the engulfment of infected apoptotic cells by bone marrowderived DCs (BMDCs) (12). Here, we sought to determine the relevance of PGE 2 synthesis in Th17 cell differentiation in the context of infected-cell efferocytosis.…”

“…When DCs take up apoptotic Escherichia coli-infected cells, they release IL-23, TGF-β, and IL-6, and induce Th17 cell differentiation (7). We recently reported that the efferocytosis of infected cells leads to PGE 2 production by DCs (12,13). PGE 2 , one of the most abundant lipid mediators produced by both immune and structural cells, acts through four different G protein-coupled receptors (14).…”