This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zeng, X. Articles by Standiford, T. J. Search for Related Content PubMed PubMed Citation Articles by Zeng, X. Articles by Standiford, T. J.

 Previous Article  |  Next Article 

Infection and Immunity, December 2005, p. 8226-8236, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.8226-8236.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Interferon-Inducible Protein 10, but Not Monokine Induced by Gamma Interferon, Promotes Protective Type 1 Immunity in Murine Klebsiella pneumoniae Pneumonia

Departments of Pathology,¹ Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical Center, Ann Arbor, Michigan,² Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts³

Received 7 June 2005/ Returned for modification 21 July 2005/ Accepted 26 August 2005

CXC chemokines that lack the ELR motif, including interferon-inducible protein 10 [IP-10 (CXCL10)] and monokine induced by gamma interferon (IFN-) [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-, whereas IP-10 was expressed in both an IFN--dependent and an IFN--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 T cells, as well as a reduction in the expression of IFN-. 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.

Editor: J. N. Weiser

This article has been cited by other articles:

• Nagarajan, U. M., Prantner, D., Sikes, J. D., Andrews, C. W. Jr., Goodwin, A. M., Nagarajan, S., Darville, T. (2008). Type I Interferon Signaling Exacerbates Chlamydia muridarum Genital Infection in a Murine Model. Infect. Immun. 76: 4642-4648 [Abstract] [Full Text]  
• Stewart, V. A., McGrath, S., Krieg, A. M., Larson, N. S., Angov, E., Smith, C. L., Brewer, T. G., Heppner, D. G. Jr. (2008). Activation of Innate Immunity in Healthy Macaca mulatta Macaques by a Single Subcutaneous Dose of GMP CpG 7909: Safety Data and Interferon-Inducible Protein-10 Kinetics for Humans and Macaques. CVI 15: 221-226 [Abstract] [Full Text]  
• Karaolis, D. K. R., Newstead, M. W., Zeng, X., Hyodo, M., Hayakawa, Y., Bhan, U., Liang, H., Standiford, T. J. (2007). Cyclic Di-GMP Stimulates Protective Innate Immunity in Bacterial Pneumonia. Infect. Immun. 75: 4942-4950 [Abstract] [Full Text]  
• Bhan, U., Lukacs, N. W., Osterholzer, J. J., Newstead, M. W., Zeng, X., Moore, T. A., McMillan, T. R., Krieg, A. M., Akira, S., Standiford, T. J. (2007). TLR9 Is Required for Protective Innate Immunity in Gram-Negative Bacterial Pneumonia: Role of Dendritic Cells. J. Immunol. 179: 3937-3946 [Abstract] [Full Text]  
• Muller, M., Carter, S. L., Hofer, M. J., Manders, P., Getts, D. R., Getts, M. T., Dreykluft, A., Lu, B., Gerard, C., King, N. J. C., Campbell, I. L. (2007). CXCR3 Signaling Reduces the Severity of Experimental Autoimmune Encephalomyelitis by Controlling the Parenchymal Distribution of Effector and Regulatory T Cells in the Central Nervous System. J. Immunol. 179: 2774-2786 [Abstract] [Full Text]  
• Fahy, O. L., Townley, S. L., McColl, S. R. (2006). CXCL16 Regulates Cell-Mediated Immunity to Salmonella enterica Serovar Enteritidis via Promotion of Gamma Interferon Production. Infect. Immun. 74: 6885-6894 [Abstract] [Full Text]