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Journal of Virology, April 2009, p. 3175-3186, Vol. 83, No. 7
0022-538X/09/$08.00+0     doi:10.1128/JVI.01907-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Dendritic Cells Are Required for Optimal Activation of Natural Killer Functions following Primary Infection with Herpes Simplex Virus Type 1{triangledown}

Sadik H. Kassim,1,4,{dagger} Naveen K. Rajasagi,1,4,{ddagger} Barry W. Ritz,2 Stephen B. Pruett,3,§ Elizabeth M. Gardner,2,¶ Robert Chervenak,1 and Stephen R. Jennings4*

Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130,1 Department of Bioscience and Biotechnology, Drexel University, Philadelphia, Pennsylvania 19104,2 Department of Cell Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130,3 Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 191294

Received 10 September 2008/ Accepted 7 January 2009

Natural killer (NK) cells play an important role in the optimal clearance of herpes simplex virus type 1 (HSV-1) infection in mice. Activated NK cells function via cytokine secretion or direct cytolysis of target cells; dendritic cells (DCs) are thought to make critical contributions in the activation of both of these functions. Yet, the magnitude and physiological relevance of DC-mediated NK cell activation in vivo is not completely understood. To examine the contribution of DC help in regulating NK cell functions after infection with HSV-1, we utilized a transgenic mouse model that allows the transient ablation of DCs. Using this approach, it was found that the gamma interferon (IFN-{gamma}) expression potential of NK cells is quantitatively and qualitatively impaired in the absence of DCs. With regard to priming of NK cytolytic functions, the ablation of DCs did not significantly affect cytotoxic protein expression by NK cells. An in vivo cytolytic assay did, however, reveal impairments in the magnitude of NK cell cytotoxicity. Overall, this study provides direct evidence that functional DCs are required for optimal IFN-{gamma} expression and cytolytic function by NK cells following infection with HSV-1.

* Corresponding author. Mailing address: Department of Microbiology and Immunology (Room 18107), Drexel University College of Medicine, 245 N. 15th Street, Philadelphia, PA 19106. Phone: (215) 762-3719. Fax: (215) 762-1955. E-mail: stephen.jennings{at}drexelmed.edu

{triangledown} Published ahead of print on 14 January 2009.

{dagger} Present address: Gene Therapy Program, University of Pennsylvania School of Medicine, Philadelphia, PA 19104.

{ddagger} Present address: Department of Microbiology, University of Tennessee, Knoxville, TN 37996.

§ Present address: Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762.

Present address: Department of Food Sciences and Human Nutrition, Michigan State University, East Lansing, MI 48824.

Journal of Virology, April 2009, p. 3175-3186, Vol. 83, No. 7
0022-538X/09/$08.00+0     doi:10.1128/JVI.01907-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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