IL48, but not IL-12, regulates NK cell activity following intranasal herpes simplex virus type I infection

被引:34
作者
Reading, Patrick C. [1 ]
Whitney, Paul G. [1 ]
Barr, Daniel P. [1 ]
Wojtasiak, Magdalena [1 ]
Mintern, Justine D. [1 ]
Waithman, Jason [1 ]
Brooks, Andrew G. [1 ]
机构
[1] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic, Australia
关键词
D O I
10.4049/jimmunol.179.5.3214
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Infection of the respiratory tract with HSV type 1 (HSV-1) can have severe clinical complications, yet little is known of the immune mechanisms that control the replication and spread of HSV-1 in this site. The present study investigated the protective role of IL-12 and IL-18 in host defense against intranasal HSV-1 infection. Both IL-12 and IL-18 were detected in lung fluids following intranasal infection of C57BL/6 (116) mice. IL-18-deficient (B6.IL-18(-/-)) mice were more susceptible to HSV-1 infection than wild-type B6 mice as evidenced by exacerbated weight loss and enhanced virus growth in the lung. IL-12-deficient (B6.IL-12(-/-)) mice behaved similarly to B6 controls. Enhanced susceptibility of B6.IL-18(-/-) mice to HSV-1 infection correlated with a profound impairment in the ability of NK cells recovered from the lungs to produce IFN-gamma or to mediate cytotoxic activity ex vivo. The weak cytotoxic capacity of NK cells from the lungs of B6.IL-18(-/-) mice correlated with reduced expression of the cytolytic effector molecule granzyme B. Moreover, depletion of NK cells from B6 or B6.IL-12-/- mice led to enhanced viral growth in lungs by day 3 postinfection; however, this treatment had no effect on viral titers in lungs of B6.IL-18(-/-) mice. Together these studies demonstrate that IL-18, but not IL-12, plays a key role in the rapid activation of NK cells and therefore in control of early FISV-I replication in the lung.
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页码:3214 / 3221
页数:8
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