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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Topical Prostaglandin E Analog Restores Defective Dendritic Cell-Mediated Th17 Host Defense Against Methicillin-Resistant Staphylococcus Aureus in the Skin of Diabetic Mice

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Author(s):
Dejani, Naiara N. ; Brandt, Stephanie L. ; Pineros, Annie ; Glosson-Byers, Nicole L. ; Wang, Sue ; Son, Young Min ; Medeiros, Alexandra I. ; Serezani, C. Henrique
Total Authors: 8
Document type: Journal article
Source: Diabetes; v. 65, n. 12, p. 3718-3729, DEC 2016.
Web of Science Citations: 9
Abstract

People with diabetes are more prone to Staphylococcus aureus skin infection than healthy individuals. Control of S. aureus infection depends on dendritic cell (DC)-induced T-helper 17 (Th17)-mediated neutrophil recruitment and bacterial clearance. DC ingestion of infected apoptotic cells (IACs) drive prostaglandin E-2 (PGE(2)) secretion to generate Th17 cells. We speculated that hyperglycemia inhibits skin DC migration to the lymph nodes and impairs the Th17 differentiation that accounts for poor skin host defense in diabetic mice. Diabetic mice showed increased skin lesion size and bacterial load and decreased PGE2 secretion and Th17 cells compared with nondiabetic mice after methicillin-resistant S. aureus (MRSA) infection. Bone marrow-derived DCs (BMDCs) cultured in high glucose (25 mmol/L) exhibited decreased Ptges mRNA expression, PGE2 production, lower CCR7-dependent DC migration, and diminished maturation after recognition of MRSA-IACs than BMDCs cultured in low glucose (5 mmol/L). Similar events were observed in DCs from diabetic mice infected with MRSA. Topical treatment of diabetic mice with the PGE analog misoprostol improved host defense against MRSA skin infection by restoring DC migration to draining lymph nodes, Th17 differentiation, and increased antimicrobial peptide expression. These findings identify a novel mechanism involved in poor skin host defense in diabetes and propose a targeted strategy to restore skin host defense in diabetes. (AU)

FAPESP's process: 11/17611-7 - Effect of efferocytosis by dendritic cells on Th17 differentiation: role of Prostaglandin E2
Grantee:Alexandra Ivo de Medeiros
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 14/17374-3 - Studying the role of PGE2/EP4/PTEN axis in Th17 differentiation during phagocytosis of infected apoptotic cells
Grantee:Naiara Naiana Dejani
Support type: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 12/23580-0 - Differentiation of Th17 cells during phagocytosis of infected apoptotic cells: determination of intracellular signaling pathways via PGE2 and EP receptors
Grantee:Naiara Naiana Dejani
Support type: Scholarships in Brazil - Doctorate