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.
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Authors | Xianying Zeng, Thomas A Moore, Michael W Newstead, Jane C Deng, Steven L Kunkel, Andrew D Luster, Theodore J Standiford |
Journal | Infection and immunity
(Infect Immun)
Vol. 73
Issue 12
Pg. 8226-36
(Dec 2005)
ISSN: 0019-9567 [Print] United States |
PMID | 16299319
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Antibodies
- Chemokine CXCL10
- Chemokine CXCL9
- Chemokines, CXC
- Cxcl9 protein, mouse
- RNA, Messenger
- Interferon-gamma
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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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