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Journal of Virology, April 2006, p. 3985-3993, Vol. 80, No. 8
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.8.3985-3993.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

In Vivo Ablation of CD11c-Positive Dendritic Cells Increases Susceptibility to Herpes Simplex Virus Type 1 Infection and Diminishes NK and T-Cell Responses

Sadik H. Kassim,1,2,3 Naveen K. Rajasagi,1,2,3 Xiangyi Zhao,3 Robert Chervenak,1 and Stephen R. Jennings1,2,3*

Department of Microbiology and Immunology,1 Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130,2 Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania 191293

Received 31 October 2005/ Accepted 25 January 2006

The precise role of each of the seven individual CD11c+ dendritic cell subsets (DCs) identified to date in the response to viral infections is not known. DCs serve as critical links between the innate and adaptive immune responses against many pathogens, including herpes simplex virus type 1 (HSV-1). The role of DCs as mediators of resistance to HSV-1 infection was investigated using CD11c-diphtheria toxin (DT) receptor-green fluorescent protein transgenic mice, in which DCs can be transiently depleted in vivo by treatment with low doses of DT. We show that ablation of DCs led to enhanced susceptibility to HSV-1 infection in the highly resistant C57BL/6 mouse strain. Specifically, we showed that the depletion of DCs led to increased viral spread into the nervous system, resulting in an increased rate of morbidity and mortality. Furthermore, we showed that ablation of DCs impaired the optimal activation of NK cells and CD4+ and CD8+ T cells in response to HSV-1. These data demonstrated that DCs were essential not only in the optimal activation of the acquired T-cell response to HSV-1 but also that DCs were crucial for innate resistance to HSV-1 infection.

* Corresponding author. Mailing address: Department of Microbiology and Immunology (G81), Drexel University College of Medicine, 2900 West Queen Ln., Philadelphia, PA 19129. Phone: (215) 991-8581. Fax: (215) 848-2271. E-mail: sjenning{at}drexelmed.edu.

Journal of Virology, April 2006, p. 3985-3993, Vol. 80, No. 8
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.8.3985-3993.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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