Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae

J Exp Med. 2005 Sep 19;202(6):761-9. doi: 10.1084/jem.20050193. Epub 2005 Sep 12.


Interleukin (IL)-23 is a heterodimeric cytokine that shares the identical p40 subunit as IL-12 but exhibits a unique p19 subunit similar to IL-12 p35. IL-12/23 p40, interferon gamma (IFN-gamma), and IL-17 are critical for host defense against Klebsiella pneumoniae. In vitro, K. pneumoniae-pulsed dendritic cell culture supernatants elicit T cell IL-17 production in a IL-23-dependent manner. However, the importance of IL-23 during in vivo pulmonary challenge is unknown. We show that IL-12/23 p40-deficient mice are exquisitely sensitive to intrapulmonary K. pneumoniae inoculation and that IL-23 p19-/-, IL-17R-/-, and IL-12 p35-/- mice also show increased susceptibility to infection. p40-/- mice fail to generate pulmonary IFN-gamma, IL-17, or IL-17F responses to infection, whereas p35-/- mice show normal IL-17 and IL-17F induction but reduced IFN-gamma. Lung IL-17 and IL-17F production in p19-/- mice was dramatically reduced, and this strain showed substantial mortality from a sublethal dose of bacteria (10(3) CFU), despite normal IFN-gamma induction. Administration of IL-17 restored bacterial control in p19-/- mice and to a lesser degree in p40-/- mice, suggesting an additional host defense requirement for IFN-gamma in this strain. Together, these data demonstrate independent requirements for IL-12 and IL-23 in pulmonary host defense against K. pneumoniae, the former of which is required for IFN-gamma expression and the latter of which is required for IL-17 production.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Cells, Cultured
  • Immunity, Cellular
  • Immunity, Innate
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / genetics
  • Interleukin-12 / deficiency
  • Interleukin-12 / genetics
  • Interleukin-12 / physiology*
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / genetics
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins / deficiency
  • Interleukins / genetics
  • Interleukins / physiology*
  • Klebsiella Infections / immunology*
  • Klebsiella Infections / prevention & control
  • Klebsiella pneumoniae / immunology*
  • Lung / immunology
  • Lung / metabolism
  • Lung / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RNA, Messenger / metabolism


  • Il23a protein, mouse
  • Interleukin-17
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins
  • RNA, Messenger
  • Interleukin-12
  • Interferon-gamma