IκBζ regulates human monocyte pro-inflammatory responses induced by Streptococcus pneumoniae

Kruthika Sundaram, Mohd Akhlakur Rahman, Srabani Mitra, Daren L. Knoell, Shireen A. Woodiga, Samantha J. King, Mark D. Wewers

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Pneumococcal lung infections represent a major cause of death worldwide. Single nucleotide polymorphisms (SNPs) in the NFKBIZ gene, encoding the transcription factor IκBζ, are associated with increased susceptibility to invasive pneumococcal disease. We hence analyzed how IκBζ might regulate inflammatory responses to pneumococcal infection. We first demonstrate that IκBζ is expressed in human blood monocytes but not in bronchial epithelial cells, in response to wild type pneumococcal strain D39. D39 transiently induced IκBζ in a dose dependent manner, with subsequent induction of downstream molecules involved in host defense. Of these molecules, IκBζ knockdown reduced the expression of IL-6 and GMCSF. Furthermore, IκBζ overexpression increased the activity of IL-6 and GMCSF promoters, supporting the knockdown findings. Pneumococci lacking either pneumolysin or capsule still induced IκBζ. While inhibition of TLR1/TLR2 blocked D39 induced IκBζ expression, TLR4 inhibition did not. Blockade of p38 MAP kinase and NFκB suppressed D39 induced IκBζ. Overall, our data demonstrates that IκBζ regulates monocyte inflammatory responses to Streptococcus pneumoniae by promoting the production of IL-6 and GMCSF.

Original languageEnglish (US)
Article numbere0161931
JournalPloS one
Volume11
Issue number9
DOIs
StatePublished - Sep 2016

Fingerprint

Streptococcus pneumoniae
interleukin-6
monocytes
Pneumococcal Infections
Monocytes
Interleukin-6
inflammation
Molecules
Gene encoding
p38 Mitogen-Activated Protein Kinases
Polymorphism
mitogen-activated protein kinase
infection
single nucleotide polymorphism
Capsules
Single Nucleotide Polymorphism
Cause of Death
epithelial cells
Blood
Transcription Factors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Sundaram, K., Rahman, M. A., Mitra, S., Knoell, D. L., Woodiga, S. A., King, S. J., & Wewers, M. D. (2016). IκBζ regulates human monocyte pro-inflammatory responses induced by Streptococcus pneumoniae. PloS one, 11(9), [e0161931]. https://doi.org/10.1371/journal.pone.0161931

IκBζ regulates human monocyte pro-inflammatory responses induced by Streptococcus pneumoniae. / Sundaram, Kruthika; Rahman, Mohd Akhlakur; Mitra, Srabani; Knoell, Daren L.; Woodiga, Shireen A.; King, Samantha J.; Wewers, Mark D.

In: PloS one, Vol. 11, No. 9, e0161931, 09.2016.

Research output: Contribution to journalArticle

Sundaram, K, Rahman, MA, Mitra, S, Knoell, DL, Woodiga, SA, King, SJ & Wewers, MD 2016, 'IκBζ regulates human monocyte pro-inflammatory responses induced by Streptococcus pneumoniae', PloS one, vol. 11, no. 9, e0161931. https://doi.org/10.1371/journal.pone.0161931
Sundaram, Kruthika ; Rahman, Mohd Akhlakur ; Mitra, Srabani ; Knoell, Daren L. ; Woodiga, Shireen A. ; King, Samantha J. ; Wewers, Mark D. / IκBζ regulates human monocyte pro-inflammatory responses induced by Streptococcus pneumoniae. In: PloS one. 2016 ; Vol. 11, No. 9.
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