Insulin Modulates the Inflammatory Granulocyte Response to Streptococci via Phosphatidylinositol 3-Kinase
| Autor: | Sandra Santos-Sierra, Julius von Süßkind-Schwendi, Timo K. van den Berg, Monika Haeffner, Sachin D. Deshmukh, Antigoni Triantafyllopoulou, Sebastian Fuchs, Philipp Henneke, Susan Farmand, Julia Wennekamp, Jochen Seufert, Miriam Mergen, Taco W. Kuijpers, Sybille Kenzel |
|---|---|
| Přispěvatelé: | Molecular cell biology and Immunology, Pediatric surgery, APH - Aging & Later Life, Amsterdam institute for Infection and Immunity, General Internal Medicine, Paediatric Infectious Diseases / Rheumatology / Immunology |
| Rok vydání: | 2012 |
| Předmět: |
Adult
Chemokine Phagocytosis medicine.medical_treatment Immunology Inflammation Granulocyte Article Streptococcus agalactiae Mice Insulin resistance medicine Animals Humans Insulin Immunology and Allergy PI3K/AKT/mTOR pathway Mice Knockout biology Kinase Infant Newborn medicine.disease Mice Inbred C57BL medicine.anatomical_structure biology.protein Insulin Resistance Phosphatidylinositol 3-Kinase medicine.symptom Granulocytes |
| Zdroj: | Kenzel, S, Mergen, M, von Süßkind-Schwendi, J, Wennekamp, J, Deshmukh, S D, Haeffner, M, Triantafyllopoulou, A, Fuchs, S, Farmand, S, Santos-Sierra, S, Seufert, J, van den Berg, T K, Kuijpers, T W & Henneke, P 2012, ' Insulin modulates the inflammatory granulocyte response to streptococci via phosphatidylinositol 3-kinase ', Journal of Immunology, vol. 189, no. 9, pp. 4582-91 . https://doi.org/10.4049/jimmunol.1200205 Journal of Immunology, 189(9), 4582-91. American Association of Immunologists Journal of immunology (Baltimore, Md., 189(9), 4582-4591. American Association of Immunologists |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1200205 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|