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Our laboratory is interested in the immunological basis for the control of infection and pathology associated with complex viral pathogens. Our principal focus has been HSV-1, which infects mucocutaneous epithelial cells and sensory neurons, and causes a lifelong latent infection in the nervous system. Our current focus is the role of the innate and acquired immune responses involved in resisting HSV-1 infection, and how these two components of immunity interact with each other to generate optimal protective responses.

Analysis of HSV-1-Specific CD8+ T Cell Responses

We have focused upon the events resulting in a potent, protective CD8+ T cell response against cutaneous HSV-1 infections. We have defined the kinetics of CD8+ T cell activation and the acquisition of effector function by this subpopulation. We know that two subpopulations of HSV-1-specific CD8+ T cells are generated during the initial response to infection: one expressing high levels of CD25 (IL-2 receptor α-chain); and a second population expressing low levels of CD25. Our current studies are investigating the relative contribution of each subpopulation to the control of infection in the skin and nervous system, their relationship to each other, the role of IL-2 and IL-15 in their development, and the contribution of each to long-term HSV-1-specific CD8+ T cell memory.  Current studies also focus on the ability of HSV-1-specific CD8+ T cells to limit infection of the central nervous system from peripheral sites.

Analysis of the Immunological Basis for Resistance to Cutaneous HSV-1 Infection

Similar to human patients infected with HSV-1 and/or HSV-2, inbred mouse strains exhibit a spectrum of susceptibility to cutaneous HSV infection. The ability to resist cutaneous HSV-1 is associated with rapid synthesis of type I IFNs (IFN-α/β) and early activation of natural killer (NK) cells, and viral clearance is dependent upon HSV-1-specific T cells. Our recent studies have focused upon the role of dendritic cells (DCs) in the intrinsic resistance to HSV-1 and determined that DCs are crucial for preventing lethal infection of the central nervous system. We are currently working on the hypothesis that certain DC subpopulations synthesize high levels of type I IFNs, which in turn activate NK cells and T cells to optimal activity. We are also investigating the role of particular HSV-1 genes to determine their role in HSV-1-mediated impairment of DC function in vivo. These studies have led to investigations of the role of certain Toll-like pattern recognition receptors (TLRs) in the innate and adaptive immune responses, and their role in limiting HSV-1 replication and spread within the peripheral and central nervous systems.

Selected Publications
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Egan KP, Allen AG, Wigdahl B, and Jennings SR
Virology, 15; 514: 124-133,  2018

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Kollias CM, Huneke RB, Wigdahl B, and Jennings SR
Journal of Neurovirology, 21: 8-23, 2015

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Egan KP, Wu S, Wigdahl B, and Jennings SR
Journal of Neurovirology, 19: 328-45, 2013

Rajasagi NK, Kassim SH, Zhao X, Chervenak R, and Jennings SR
Journal of Virology, 83: 5256-5268, 2009

Kassim SH, Rajasagi NK, Ritz B, Pruett SB, Chervenak R, and Jennings SR
Journal of Virology, 83: 3175-3186, 2009

Borowski AB, Boesteanu AC, Mueller YM, Carafides C, Topham DJ, Altman JD, Jennings SR, and Katsikis PD
The Journal of Immunology, 179(10): 6494-6503, 2007

Jain P, Ahuja J, Khan ZK, Shimzu S, Meucci O, Kampani K, Jennings SR, and Wighdahl B
Journal of Leukocyte Biology, 82: 44-56, 2007

Kassim SH, Rajasagi NK, Zhao X, Chervenak R, and Jennings SR
Journal of Virology, 80: 3985-3993, 2006

Zhang Y, Smith PM, Frampton AR, Osterrieder N, Jennings SR, and O'Callaghan DJ
Viral Immunology, 16: 307-320, 2003

Oshima T, Laroux FS, Coe LL, Morise Z, Kawachi S, Bauer P, Grisham MB, Specian RD, Carter P, Jennings SR, "Granger DN, Joh T, and Alexander JS
Microvascular Research, 61: 130-143, 2000

Vallien G, Langley R, Jennings SR, Specian R, and Granger DN
Microcirculation, 7: 249-258, 2000

Smith PM, Zhang YF, Grafton WD, Jennings SR, and O'Callaghan DJ
Journal of Virology, 74: 10034-10040, 2000

Kawachi S, Morise Z, Jennings SR, Conner E, Cockrell A, Laroux FS, Chervenak R, Wolcott M, van der Heyde H, Gray L, Feng L, Granger N, Specian RD, and Grisham MB
Inflammatory Bowel Disease, 6: 171-180, 2000

Andersen H, Dempsey D, Chervenak R, and Jennings SR
The Journal of Immunology, 165: 2101-2107, 2000

"Determination of specific antibody-secreting cells following immunization with EHV-1 KyA and recombinant glycoprotein D by ELISPOT in CBA mice"
Zhang YF, Smith PM, Jennings SR, and O'Callaghan DJ
Virology, 268: 482-492, 2000

Jones CM, Cose SC, McNally JM, Jennings SR, Heath WR, and Carbone FR
Journal of General Virology, 81: 407-414, 2000

McNally JM, Andersen HA, Chervenak R, and Jennings SR
Cellular Immunology, 194: 103-111, 1999

McNally JM, Dempsey D, Wolcott RM, Chervenak R, and Jennings SR
The Journal of Immunology, 163: 675-681, 1999