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
Kenzel, Sybille ; Mergen, Miriam ; von Süßkind-Schwendi, Julius ; Wennekamp, Julia ; Deshmukh, Sachin D ; Haeffner, Monika ; Triantafyllopoulou, Antigoni ; Fuchs, Sebastian ; Farmand, Susan ; Santos-Sierra, Sandra ; Seufert, Jochen ; van den Berg, Timo K ; Kuijpers, Taco W ; Henneke, Philipp. / Insulin modulates the inflammatory granulocyte response to streptococci via phosphatidylinositol 3-kinase. In: Journal of Immunology. 2012 ; Vol. 189, No. 9. pp. 4582-91.
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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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author = "Sybille Kenzel and Miriam Mergen and {von S{\"u}{\ss}kind-Schwendi}, Julius and Julia Wennekamp and Deshmukh, {Sachin D} and Monika Haeffner and Antigoni Triantafyllopoulou and Sebastian Fuchs and Susan Farmand and Sandra Santos-Sierra and Jochen Seufert and {van den Berg}, {Timo K} and Kuijpers, {Taco W} and Philipp Henneke",
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Kenzel, S, Mergen, M, von Süßkind-Schwendi, J, Wennekamp, J, Deshmukh, SD, Haeffner, M, Triantafyllopoulou, A, Fuchs, S, Farmand, S, Santos-Sierra, S, Seufert, J, van den Berg, TK, Kuijpers, TW & 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

Insulin modulates the inflammatory granulocyte response to streptococci via phosphatidylinositol 3-kinase. / Kenzel, Sybille; Mergen, Miriam; von Süßkind-Schwendi, Julius; Wennekamp, Julia; Deshmukh, Sachin D; Haeffner, Monika; Triantafyllopoulou, Antigoni; Fuchs, Sebastian; Farmand, Susan; Santos-Sierra, Sandra; Seufert, Jochen; van den Berg, Timo K; Kuijpers, Taco W; Henneke, Philipp.

In: Journal of Immunology, Vol. 189, No. 9, 01.11.2012, p. 4582-91.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Insulin modulates the inflammatory granulocyte response to streptococci via phosphatidylinositol 3-kinase

AU - Kenzel, Sybille

AU - Mergen, Miriam

AU - von Süßkind-Schwendi, Julius

AU - Wennekamp, Julia

AU - Deshmukh, Sachin D

AU - Haeffner, Monika

AU - Triantafyllopoulou, Antigoni

AU - Fuchs, Sebastian

AU - Farmand, Susan

AU - Santos-Sierra, Sandra

AU - Seufert, Jochen

AU - van den Berg, Timo K

AU - Kuijpers, Taco W

AU - Henneke, Philipp

PY - 2012/11/1

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N2 - 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.

AB - 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.

KW - Adult

KW - Animals

KW - Granulocytes/enzymology

KW - Humans

KW - Infant, Newborn

KW - Inflammation/immunology

KW - Insulin/pharmacology

KW - Insulin Resistance/immunology

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Phosphatidylinositol 3-Kinase/physiology

KW - Streptococcus agalactiae/immunology

U2 - 10.4049/jimmunol.1200205

DO - 10.4049/jimmunol.1200205

M3 - Article

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SP - 4582

EP - 4591

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

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Kenzel S, Mergen M, von Süßkind-Schwendi J, Wennekamp J, Deshmukh SD, Haeffner M et al. Insulin modulates the inflammatory granulocyte response to streptococci via phosphatidylinositol 3-kinase. Journal of Immunology. 2012 Nov 1;189(9):4582-91. https://doi.org/10.4049/jimmunol.1200205