Group B streptococci induce proinflammatory responses via a protein kinase D1-dependent pathway

Kirtikumar Upadhyay, Jeoung Eun Park, Tae Won Yoon, Priyanka Halder, Young In Kim Hoehamer, Victoria Metcalfe, Ajay Talati, B. Keith English, Ae-Kyung Yi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Group B streptococci (GBS) are one of the leading causes of life-threatening illness in neonates. Proinflammatory responses to GBS mediated through host innate immune receptors play a critical role in the disease manifestation. However, the mechanisms involved in proinflammatory responses against GBS, as well as the contribution of signaling modulators involved in host immune defense, have not been fully elucidated. In the present study, we investigated the role of protein kinase D (PKD)1 in the proinflammatory responses to GBS.We found that both live and antibiotic-killed GBS induce activation of PKD1 through a pathway that is dependent on the TLR signaling adaptor MyD88 and its downstream kinase IL-1R-associated kinase 1, but independent of TNFR-associated factor 6. Our studies using pharmacological PKD inhibitors and PKD1-knockdown macrophages revealed that PKD1 is indispensable for GBS-mediated activation of MAPKs and NF-kB and subsequent expression of proinflammatory mediators. Furthermore, systemic administration of a PKD inhibitor protects D-galactosamine-sensitized mice from shock-mediated death caused by antibiotic-killed GBS. These findings imply that PKD1 plays a critical regulatory role in GBS-induced proinflammatory reactions and sepsis, and inhibition of PKD1 activation together with antibiotic treatment in GBS-infected neonates could be an effective way to control GBS diseases.

Original languageEnglish (US)
Pages (from-to)4448-4457
Number of pages10
JournalJournal of Immunology
Volume198
Issue number11
DOIs
StatePublished - Jun 1 2017

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Streptococcus agalactiae
Protein Kinases
Protein Kinase Inhibitors
Anti-Bacterial Agents
Phosphotransferases
Galactosamine
NF-kappa B
Streptococcus
Shock
Sepsis
Macrophages
Pharmacology
Control Groups

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Upadhyay, K., Park, J. E., Yoon, T. W., Halder, P., Kim Hoehamer, Y. I., Metcalfe, V., ... Yi, A-K. (2017). Group B streptococci induce proinflammatory responses via a protein kinase D1-dependent pathway. Journal of Immunology, 198(11), 4448-4457. https://doi.org/10.4049/jimmunol.1601089

Group B streptococci induce proinflammatory responses via a protein kinase D1-dependent pathway. / Upadhyay, Kirtikumar; Park, Jeoung Eun; Yoon, Tae Won; Halder, Priyanka; Kim Hoehamer, Young In; Metcalfe, Victoria; Talati, Ajay; English, B. Keith; Yi, Ae-Kyung.

In: Journal of Immunology, Vol. 198, No. 11, 01.06.2017, p. 4448-4457.

Research output: Contribution to journalArticle

Upadhyay, K, Park, JE, Yoon, TW, Halder, P, Kim Hoehamer, YI, Metcalfe, V, Talati, A, English, BK & Yi, A-K 2017, 'Group B streptococci induce proinflammatory responses via a protein kinase D1-dependent pathway', Journal of Immunology, vol. 198, no. 11, pp. 4448-4457. https://doi.org/10.4049/jimmunol.1601089
Upadhyay K, Park JE, Yoon TW, Halder P, Kim Hoehamer YI, Metcalfe V et al. Group B streptococci induce proinflammatory responses via a protein kinase D1-dependent pathway. Journal of Immunology. 2017 Jun 1;198(11):4448-4457. https://doi.org/10.4049/jimmunol.1601089
Upadhyay, Kirtikumar ; Park, Jeoung Eun ; Yoon, Tae Won ; Halder, Priyanka ; Kim Hoehamer, Young In ; Metcalfe, Victoria ; Talati, Ajay ; English, B. Keith ; Yi, Ae-Kyung. / Group B streptococci induce proinflammatory responses via a protein kinase D1-dependent pathway. In: Journal of Immunology. 2017 ; Vol. 198, No. 11. pp. 4448-4457.
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