Insulin modulates the inflammatory granulocyte response to streptococci via phosphatidylinositol 3-kinase

Sybille Kenzel, Miriam Mergen, Julius von Süßkind-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

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)4582-91
Number of pages10
JournalJournal of Immunology
Volume189
Issue number9
DOIs
Publication statusPublished - 1 Nov 2012

Cite this

Kenzel, S., Mergen, M., von Süßkind-Schwendi, J., Wennekamp, J., Deshmukh, S. D., Haeffner, M., ... Henneke, P. (2012). Insulin modulates the inflammatory granulocyte response to streptococci via phosphatidylinositol 3-kinase. Journal of Immunology, 189(9), 4582-91. https://doi.org/10.4049/jimmunol.1200205