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

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 den...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of experimental medicine 2005-09, Vol.202 (6), p.761-769
Main Authors: Happel, Kyle I, Dubin, Patricia J, Zheng, Mingquan, Ghilardi, Nico, Lockhart, Christie, Quinton, Lee J, Odden, Anthony R, Shellito, Judd E, Bagby, Gregory J, Nelson, Steve, Kolls, Jay K
Format: Article
Language:English
Subjects:
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
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20050193