Insulin Modulates the Inflammatory Granulocyte Response to Streptococci Via Phosphatidylinositol 3-kinase

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2012 Sep 29

PMID 23018458

Citations 8

Authors

Sybille Kenzel

Miriam Mergen

Julius von Susskind-Schwendi

Julia Wennekamp

Sachin D Deshmukh

Monika Haeffner

Antigoni Triantafyllopoulou

Sebastian Fuchs

Susan Farmand

Sandra Santos-Sierra

Jochen Seufert

Timo K van den Berg

Taco W Kuijpers

Philipp Henneke

Affiliations

Soon will be listed here.

Abstract

Group B streptococci (GBS; Streptococcus agalactiae) are a major cause of invasive infections in newborn infants and in patients with type 2 diabetes. Both patient groups exhibit peripheral insulin resistance and alterations in polymorphonuclear leukocyte (PML) function. In this investigation, we studied the PML response repertoire to GBS with a focus on TLR signaling and the modulation of this response by insulin in mice and humans. We found that GBS-induced, MyD88-dependent chemokine formation of PML was specifically downmodulated by insulin via insulin receptor-mediated induction of PI3K. PI3K inhibited transcription of chemokine genes on the level of NF-κB activation and binding. Insulin specifically modulated the chemokine response of PML to whole bacteria, but affected neither activation by purified TLR agonists nor antimicrobial properties, such as migration, phagocytosis, bacterial killing, and formation of reactive oxygen species. The targeted modulation of bacteria-induced chemokine formation by insulin via PI3K may form a basis for the development of novel targets of adjunctive sepsis therapy.

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