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Interferon-inducible protein 10, but not monokine induced by gamma interferon, promotes protective type 1 immunity in murine Klebsiella pneumoniae pneumonia.

Abstract
CXC chemokines that lack the ELR motif, including interferon-inducible protein 10 [IP-10 (CXCL10)] and monokine induced by gamma interferon (IFN-gamma) [MIG (CXCL9)], have been shown to mediate the generation of type 1 immune responses. In this study, we found that intrapulmonary administration of the gram-negative bacterium Klebsiella pneumoniae resulted in the local and systemic expression of IP-10, followed sequentially by MIG expression. MIG mRNA expression in the lungs of Klebsiella-infected mice required the endogenous production of IFN-gamma, whereas IP-10 was expressed in both an IFN-gamma-dependent and an IFN-gamma-independent fashion. Antibody-mediated neutralization of IP-10 resulted in reduced bacterial clearance and decreased survival, whereas bacterial clearance was unaltered in mice treated with anti-MIG antibody. Impaired bacterial clearance in anti-IP-10 antibody-treated mice was associated with significant reductions in the number and/or activational status of NK and NK-T cells, CD4+ T cells, and gammadelta T cells, as well as a reduction in the expression of IFN-gamma. Conversely, the transient transgenic expression of murine IP-10 using adenovirus-mediated gene transfer resulted in improved bacterial clearance when IP-10 adenovirus was given concomitant with intrapulmonary bacterial challenge. These results indicate that IP-10 is an important component of innate immunity against extracellular bacterial pathogens of the lung and may represent a candidate molecule for immunotherapy in the setting of severe respiratory tract infection.
AuthorsXianying Zeng, Thomas A Moore, Michael W Newstead, Jane C Deng, Steven L Kunkel, Andrew D Luster, Theodore J Standiford
JournalInfection and immunity (Infect Immun) Vol. 73 Issue 12 Pg. 8226-36 (Dec 2005) ISSN: 0019-9567 [Print] United States
PMID16299319 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Antibodies
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Chemokines, CXC
  • Cxcl9 protein, mouse
  • RNA, Messenger
  • Interferon-gamma
Topics
  • Adenoviridae (genetics)
  • Animals
  • Antibodies (administration & dosage, pharmacology)
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Chemokines, CXC (genetics, metabolism, physiology)
  • Female
  • Immunity, Innate (genetics)
  • Interferon-gamma (genetics, metabolism)
  • Klebsiella Infections (immunology, metabolism)
  • Klebsiella pneumoniae
  • Leukocytes (microbiology)
  • Lung (immunology, microbiology, pathology)
  • Male
  • Mice
  • Mice, Knockout
  • Pneumonia, Bacterial (immunology, metabolism)
  • RNA, Messenger (analysis, metabolism)

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