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Loss of Mandibular Lymph Node Integrity Is Associated with an Increase in Sensitivity to HSV-1 Infection in CD118-Deficient Mice¹

Christopher D. Conrady^*, Manoj Thapa^*, Todd Wuest^* and Daniel J. J. Carr^2,

^* Departments of Microbiology, Immunology, and Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104

Type I IFNs are potent antiviral cytokines that contribute to the development of the adaptive immune response. To determine the role of type I IFNs in this process in an infectious disease model, mice deficient in the type I IFN receptor (CD118^–/–) were ocularly infected with HSV-1 and surveyed at times post infection in the nervous system and lymph node for virus and the host immune response. Virus titers were elevated in the trigeminal ganglia and brain stem with virus disseminating rapidly to the draining lymph node of CD118^–/– mice. T cell and plasmacytoid dendritic cell infiltration into the brain stem was reduced in CD118^–/– mice following infection, which correlated with a reduction in CXCL10 but not CXCL9 expression. In contrast, CXCL1 and CCL2 levels were up-regulated in the brainstem of CD118^–/– mice associated with an increase in F4/80⁺ macrophages. By day 5 post infection, there was a significant loss in T, NK, and plasmacytoid dendritic cell numbers in the draining lymph nodes associated with an increase in apoptotic/necrotic T cells and an appreciable lack of HSV-specific CD8⁺ T cells. The adoptive transfer of HSV-specific TCR transgenic CD8⁺ T cells into CD118^–/– mice at the time of infection modestly reduced viral titers in the nervous system suggesting in addition to the generation of HSV-specific CD8⁺ T cells, other type I IFN-activated pathways are instrumental in controlling acute infection.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Principal support for this work is by NIH R01 AI053108 (to D.J.J.C.). Additional support includes P20 RR017703, NEI core Grant EY12190, and an unrestricted grant from Research to Prevent Blindness.

² Address correspondence and reprint requests to Dr. Daniel J. J. Carr, Department of Ophthalmology, Room 415, University of Oklahoma Health Sciences Center, 608 Stanton L. Young Boulevard, Oklahoma City, OK 73104. E-mail address: dan-carr{at}ouhsc.edu

³ Abbreviations used in this paper: WT, wild type; DC, dendritic cell; MLN, mandibular lymph nodes; pi, post infection; TG, trigeminal ganglia; BS, brain stem; gB, glycoprotein B.