| First Author | Zeng X | Year | 2005 |
| Journal | Infect Immun | Volume | 73 |
| Issue | 12 | Pages | 8226-36 |
| PubMed ID | 16299319 | Mgi Jnum | J:104304 |
| Mgi Id | MGI:3611647 | Doi | 10.1128/IAI.73.12.8226-8236.2005 |
| Citation | Zeng X, et al. (2005) Interferon-inducible protein 10, but not monokine induced by gamma interferon, promotes protective type 1 immunity in murine Klebsiella pneumoniae pneumonia. Infect Immun 73(12):8226-36 |
| abstractText | 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. |
