Anthony R. French, Ph.D., M.D.

Associate Professor
Pathology and Immunology
Biomedical Engineering

Immunology Program
Molecular Microbiology and Microbial Pathogenesis Program

Research Abstract:

Natural killer cells play a crucial role in anti-pathogen host defense and are particularly important in mediating resistance to viral infections. Abnormalities in either NK cell numbers and/or function have also been consistently identified in a number of autoimmune disorders such as rheumatoid arthritis. Our laboratory focuses on understanding in vivo NK responses by studying NK cells during viral infections. Murine resistance to two herpesviruses, murine cytomegalovirus (MCMV) and herpes simplex virus- type 1 (HSV-1), as well as to the poxvirus ectromelia has been genetically mapped to the natural killer gene complex on mouse chromosome 6 which encodes a substantial fraction of the mouse NK cell receptors. Using MCMV as well as with HSV-1 and a prototypical poxvirus, vaccinia, we are addressing the following research aims:
1) Characterizing the in vivo proliferative responses of natural killer (NK) cells during viral infections with particular focus on the contributions of IFNα/β, IL-15, and IL-18.
2) Understanding the homeostasis of NK cells in mice following viral infections.
3) Exploiting the immunoevasion of DNA viruses in immunocompromised hosts to delineate novel innate immune responses including NK cell interactions with viral encoded proteins.
4) Determining the specific NK cell activation receptors involved in NK cell mediated resistance to large DNA viruses such as vaccinia and herpes simplex virus.

Selected Publications:

Zhao YM, French AR. Mechanistic model of natural killer cell proliferative response to IL-15 receptor stimulation. PLOS Computational Biology 2013; in press.

Fogel LA, Sun MM, Geurs TL, Carayannopoulous LN, French AR. Markers of nonselective and specific NK cell activation. J Immunol 2013; 190:6269-76.

Ornstein BW, Hill EB, Geurs TL, French AR. Natural killer cell functional defects in pediatric patients with severe and recurrent herpesvirus infections. J Infect Dis 2013; 207:458-468.

Zhao, YM and AR French. Two-Compartment Model of Natural Killer Cell Proliferation: Insight from Population Response to IL-15 Stimulation. J Immunol 2012; 188:2981-90.

Geurs TL, EL Hill, DM Lippold, AR French. Sex Differences in Murine Susceptibility to Systemic Viral Infections. J Autoimmunity 2012; 38:J245-53.

Campbell JA, Davis RS, Lilly LM, Fremont DH, French* AR, Carayannopoulos LN. Cutting Edge: FcRL5 on Innate B Cells is Targeted by a Poxvirus MHC Class i-like Immunoevasin. J Immunl 2010: 185:28-32 (*corresponding author).

Geurs TL, Zhao YM, Hill EB, French AR. Ly49H Engagement Compensates for the Absence of Type I Interferon Signaling in STimulating NK Cell Proliferation during MCMV Infection. J Immunol 2009 183: 5830-5836.

Fehniger TA, Cai SF, Xuefang C, Bredemeyer AJ, Presti RM, French* AR, Ley TJ. Murine NK cells contain abundant granzyme B and perforin mRNAs with minimal protein: activation leads to translation and cytotoxicity. Immunity 2007 26: 798-811 (*co-corresponding author).

French AR, Pingel JT, Wagner M, Bubic I, Yang L, Kim S, Koszinowski U, Jonjic S, Yokoyama WM. Escape of mutant double-stranded DNA virus from innate immune control. Immunity 2004 20: 747-756.

Krug A, French AR, Barchet W, Fischer J, Dzionek A, Pingel JT, Akira S, Yokoyama WM, Colonna M. TLR9-dependent recognition of murine cytomegalovirus (MCMV) by interferon-producing cell and dendritic cells generates a coordinated cytokine response that activates anti-viral NK cell function. Immunity 2004 21: 107-119.

Last Updated: 8/7/2013 2:37:13 PM

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