Intracellular bacteria recognition contributes to maximal interleukin (IL)-12 production by IL-10-deficient macrophages

H. Naruse, T. Hisamatsu, Y. Yamauchi, J. E. Chang, K. Matsuoka, M. T. Kitazume, K. Arai, S. Ando, Takanori Kanai, N. Kamada, T. Hibi

Research output: Contribution to journalArticle

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Abstract

Interleukin (IL)-12 is a key factor that induces T helper cell type 1-mediated immunity and inflammatory diseases. In some colitis models, such as IL-10 knock-out (KO) mice, IL-12 triggers intestinal inflammation. An abundant amount of IL-12 is produced by intestinal macrophages in response to stimulation by commensal bacteria in IL-10 KO mice. Intact bacteria are more potent inducers of macrophage IL-12 production than cell surface components in this model. This suggested that cell surface receptor signalling and intracellular pathogen recognition mechanisms are important for the induction of IL-12. We addressed the importance of intracellular recognition mechanisms and demonstrated that signal transducers and activator of transcription 1 (STAT1) signalling activated bacterial phagocytosis and was involved in the induction of abnormal IL-12 production. In IL-10 KO mouse bone marrow-derived (BM) macrophages, Escherichia coli stimulation induced increased IL-12p70 production compared to lipopolysaccharide combined with interferon (IFN)-γ treatment. Significant repression of IL-12 production was achieved by inhibition of phagocytosis with cytochalasin D, and inhibition of de novo protein synthesis with cycloheximide. Induction of IFN regulatory factors-1 and -8, downstream molecules of STAT1 and the key transcription factors for IK-12 transcription, following E. coli stimulation, were mediated by phagocytosis. Interestingly, STAT1 was activated after stimulation with E. coli in IL-10 KO BM macrophages, although IFN-γ could not be detected. These data suggest that molecules other than IFN-γ are involved in hyper-production mechanisms of IL-12 induced by E. coli stimulation. In conclusion, enteric bacteria stimulate excessive IL-12p70 production in IL-10 KO BM macrophages via phagocytosis-dependent signalling.

Original languageEnglish
Pages (from-to)137-144
Number of pages8
JournalClinical and Experimental Immunology
Volume164
Issue number1
DOIs
Publication statusPublished - 2011 Apr

Fingerprint

Interleukin-12
Interleukin-10
Macrophages
Bacteria
STAT1 Transcription Factor
Phagocytosis
Knockout Mice
Interferons
Escherichia coli
Interleukins
Interferon Regulatory Factor-1
Cytochalasin D
Cell Surface Receptors
Enterobacteriaceae
Cellular Structures
Colitis
Cycloheximide
Interleukin-1
Cellular Immunity
Lipopolysaccharides

Keywords

  • Bacteria
  • IL-10
  • IL-12
  • Macrophage
  • Phagocytosis

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Intracellular bacteria recognition contributes to maximal interleukin (IL)-12 production by IL-10-deficient macrophages. / Naruse, H.; Hisamatsu, T.; Yamauchi, Y.; Chang, J. E.; Matsuoka, K.; Kitazume, M. T.; Arai, K.; Ando, S.; Kanai, Takanori; Kamada, N.; Hibi, T.

In: Clinical and Experimental Immunology, Vol. 164, No. 1, 04.2011, p. 137-144.

Research output: Contribution to journalArticle

Naruse, H, Hisamatsu, T, Yamauchi, Y, Chang, JE, Matsuoka, K, Kitazume, MT, Arai, K, Ando, S, Kanai, T, Kamada, N & Hibi, T 2011, 'Intracellular bacteria recognition contributes to maximal interleukin (IL)-12 production by IL-10-deficient macrophages', Clinical and Experimental Immunology, vol. 164, no. 1, pp. 137-144. https://doi.org/10.1111/j.1365-2249.2011.04318.x
Naruse, H. ; Hisamatsu, T. ; Yamauchi, Y. ; Chang, J. E. ; Matsuoka, K. ; Kitazume, M. T. ; Arai, K. ; Ando, S. ; Kanai, Takanori ; Kamada, N. ; Hibi, T. / Intracellular bacteria recognition contributes to maximal interleukin (IL)-12 production by IL-10-deficient macrophages. In: Clinical and Experimental Immunology. 2011 ; Vol. 164, No. 1. pp. 137-144.
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AU - Matsuoka, K.

AU - Kitazume, M. T.

AU - Arai, K.

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