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

X Zeng, TA Moore, MW Newstead, JC Deng… - Infection and …, 2005 - Am Soc Microbiol
X Zeng, TA Moore, MW Newstead, JC Deng, SL Kunkel, AD Luster, TJ Standiford
Infection and immunity, 2005Am Soc Microbiol
ABSTRACT CXC chemokines that lack the ELR motif, including interferon-inducible protein
10 [IP-10 (CXCL10)] and monokine induced by gamma interferon (IFN-γ)[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 …
Abstract
CXC chemokines that lack the ELR motif, including interferon-inducible protein 10 [IP-10 (CXCL10)] and monokine induced by gamma interferon (IFN-γ) [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-γ, whereas IP-10 was expressed in both an IFN-γ-dependent and an IFN-γ-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 γδ T cells, as well as a reduction in the expression of IFN-γ. 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.
American Society for Microbiology