+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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

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

Proceedings of the National Academy of Sciences of the United States of America 115(36): E8469-E8478

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, PGE2, 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 Escherichia coli-infected macrophages by dendritic cells triggers PGE2 production in addition to pro-Th17 cytokine expression. We therefore examined the role of PGE2 during Th17 differentiation and intestinal pathology. The efferocytosis of apoptotic E. coli-infected cells by dendritic cells promoted high levels of PGE2, which impaired IL-1R expression via the EP4-PKA pathway in T cells and consequently inhibited Th17 differentiation. The outcome of murine intestinal Citrobacter rodentium infection was dependent on the EP4 receptor. Infected mice treated with EP4 antagonist showed enhanced intestinal defense against C. rodentium 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.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 065251736

Download citation: RISBibTeXText

PMID: 30127026

DOI: 10.1073/pnas.1722016115

Related references

Nitric oxide production by human intestinal epithelial cells and competition for arginine as potential determinants of host defense against the lumen-dwelling pathogen Giardia lamblia. Journal of Immunology Baltimore 164(3): 1478-1487, 2000

Flagellin-independent regulation of chemokine host defense in Campylobacter jejuni-infected intestinal epithelium. Infection and Immunity 74(6): 3437-3447, 2006

Differential expression of intestinal nutrient transporters and host defense peptides in Eimeria maxima-infected Fayoumi and Ross chickens. Poultry Science 2018, 2018

Reciprocal interactions between T cells and intestinal muscle cells; Role of IL-4 in host defense. Gastroenterology 112(4 SUPPL ): A997, 1997

Implications of early apoptosis of infected cells as an important host defense. Medical Hypotheses 54(4): 591-596, 2000

Efferocytosis of Pathogen-Infected Cells. Frontiers in Immunology 8: 1863, 2018

The interaction of intestinal epithelial cells and intraepithelial lymphocytes in host defense. Immunologic Research 20(3): 219-235, 2000

Unique intestinal cytotoxic cells associated with host defense to coccidiosis: a review. Coccidia and intestinal coccidiomorphs Proceedings of the Vth International Coccidiosis Conference Tours France, 17-20 October 1989: 577-589, 1989

Protein S and Gas6 induce efferocytosis of HIV-1-infected cells. Virology 515: 176-190, 2018

Protein S and Gas6 induce efferocytosis of HIV-1-infected cells. Virology 515: 176-190, 2018

Neutrophil-mediated dissolution of infected host cells as a defense strategy against a facultative intracellular bacterium. Journal of Experimental Medicine 174(3): 741-744, 1991

The role of human intestinal paneth cells expressing toll like receptors in innate host defense. Digestive Disease Week Abstracts & Itinerary Planner : Abstract No 357, 2003

Activation of p38α in T cells regulates the intestinal host defense against attaching and effacing bacterial infections. Journal of Immunology 191(5): 2764-2770, 2013

Deoxynivalenol Impairs Porcine Intestinal Host Defense Peptide Expression in Weaned Piglets and IPEC-J2 Cells. Toxins 10(12), 2018

O-antigen delays lipopolysaccharide recognition and impairs antibacterial host defense in murine intestinal epithelial cells. Plos Pathogens 5(9): E1000567, 2009