IL-18, but not IL-12, regulates NK cell activity following intranasal herpes simplex virus type 1 infection.
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 (B6) 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 HSV-1 replication in the lung.
Reading
Patrick C
PC
Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia. preading@unimelb.edu.au
Whitney
Paul G
PG
Barr
Daniel P
DP
Wojtasiak
Magdalena
M
Mintern
Justine D
JD
Waithman
Jason
J
Brooks
Andrew G
AG
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology / Q000821:virology; D006561:Herpes Simplex / Q000276:immunology*; D018259:Herpesvirus 1, Human; D018664:Interleukin-12 / Q000032:analysis / Q000235:genetics / Q000502:physiology; D020382:Interleukin-18 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D011024:Pneumonia, Viral / Q000276:immunology*
D020382:Interleukin-18; D018664:Interleukin-12