David G. Brooks, Ph.D.

Mailing Address:
BOX 957364, 290A BSRB
Los Angeles, CA 90095

Work Address:
290A BSRB
Los Angeles, CA 90095

Affiliations
Affiliations
Assistant Professor, Microbiology, Immunology & Molecular Genetics
Member, CTSI, Tumor Immunology Program at the Jonsson Comprehensive Cancer Center (JCCC)
Research Interests
Persistent viral infections are one of the greatest health concerns worldwide and the treatment of these infections represents a major challenge to medical science. T cell responses are crucial to prevent and control viral infections. However, T cell activity is rapidly lost following persistent viral infections. Therapies to cure persistent infections have largely been unsuccessful because it is unclear exactly why the immune response initially fails to eliminate infection and what is required of the immune system to purge virus once it proceeds past acute infection. My laboratory is focused on understanding the mechanisms of viral pathogenesis and immunity that lead to effective virus clearance versus viral persistence. In particular, we are interested in the interplay between the myriad of signals and factors that program T cell immunity and how they culminate in distinct functional outcomes. In order to understand the mechanisms that lead to divergent T cell responses my laboratory uses the lymphocytic choriomeningitis virus (LCMV) model of murine infection. LCMV is an excellent model for exploratory studies in virus: host interactions and has served as a prototype for dissecting the success or failure of immune responses in acute and persistent infections. The LCMV model enables the use of genetic tools (i.e., gene knock-out or knock-in mice), antibody depletion protocols and the visualization of virus-specific T cells in vivo that are not feasible in human/ non-human primate models of infection. A major benefit of the LCMV system is that it allows direct comparison of two genetically similar viral variants that cause very different infections. Infection with LCMV-Armstrong (Arm) stimulates robust antiviral T cell responses that clear infection within 8-10 days and generates memory T cells that protect against subsequent re-challenge. LCMV-Clone 13 (Cl 13) aborts T cell activity leading to a persistent infection. Importantly, LCMV-Arm and Cl 13 share identical CD4 and CD8 T cell epitopes providing the unique opportunity to directly compare the same T cell responses during an acute versus persistent virus infection. Most recently we have implemented this system to establish that host-mediated immunosuppressive mechanisms are invoked rapidly after infection with persisting viruses directly leading to the loss of T cell function and the inability to clear infection. Therapeutic blockade of these immunosuppressive factors rapidly restores T cell activity eliminating persistent infection. Current projects in the laboratory include identifying the regulatory factors that program productive versus abortive T cells responses, defining the factors that sustain T cell immunity during periods of viral persistence and imaging immune cells and the immunosuppressive interactions that lead to viral persistence in vivo. Our laboratory is additionally interested in molecularly defining CD4 T cell help and exploring the precise mechanisms of CD4 T cell help that program functional memory T cell differentiation following an acute infection and that sustain antiviral T cell activity to control persistent viral infection. Ultimately, our hope is that the elucidation of these mechanisms will aid in the development of novel targeted-vaccine strategies that enhance immunity, prevent infection and therapeutically correct immune dysfunction to control persistent viral infections.
Publications

A selected list of publications:

Garidou Lucile, Heydari Sara, Truong Phi, Brooks David G, McGavern Dorian B   Therapeutic memory T cells require costimulation for effective clearance of a persistent viral infection Journal of virology, 2009; 83(17): 8905-15.
Brooks, D.G., Lee, A.M., Elsaesser, H., McGavern, D.B. and Oldstone, M.B.A.   IL-10 blockade facilitates DNA vaccine-induced T cell responses and enhances clearance of persistent virus infection, Journal of Experimental Medicine, 2008; 205: 533-541.
Brooks, D.G., Trifilo, M.J., Edelmann, K.H., Teyton, L., McGavern, D.B. and Oldstone, M.B.A.   Interleukin-10 determines viral clearance or persistence in vivo, Nature Medicine, 2006; 12: 1301-1309.
Brooks, D.G., McGavern, D.B. and Oldstone, M.B.A.   Re-programming of antiviral T cells prevents inactivation and restores T cell activity during persistent viral infection, Journal of Clinical Investigation, 2006; 161: 1675-1685.
Brooks, D.G., Teyton, L, Oldstone, M.B.A. and McGavern, D.B.   Intrinsic functional dysregulation of CD4 T cell occurs rapidly during persistent viral infection, Journal of Virology, 2005; 79: 10514-10527.
Wilson Elizabeth B, Brooks David G   The role of IL-10 in regulating immunity to persistent viral infections Current topics in microbiology and immunology, 2011; 350(Pt 1): 39-65.
Brooks David G, Ha Sang-Jun, Elsaesser Heidi, Sharpe Arlene H, Freeman Gordon J, Oldstone Michael B A   IL-10 and PD-L1 operate through distinct pathways to suppress T-cell activity during persistent viral infection Proceedings of the National Academy of Sciences of the United States of America, 2008; 105(51): 20428-33.
Brooks David G   Suppressing the suppressor Blood, 2009; 114(2): 233.
Brooks David   Social animal: how the new sciences of human nature can help make sense of a life New Yorker (New York, N.Y. : 1925), 2011; 350(Pt 1): 26-32.
Tomassian Tamar, Humphries Lisa A, Liu Scot D, Silva Oscar, Brooks David G, Miceli M Carrie   Caveolin-1 orchestrates TCR synaptic polarity, signal specificity, and function in CD8 T cells Journal of immunology (Baltimore, Md. : 1950), 2011; 187(6): 2993-3002.
Wilson Elizabeth B, Kidani Yoko, Elsaesser Heidi, Barnard Jennifer, Raff Laura, Karp Christopher L, Bensinger Steven, Brooks David G   Emergence of Distinct Multiarmed Immunoregulatory Antigen-Presenting Cells during Persistent Viral Infection Cell host & microbe, 2012; 11(5): 481-91.
Elsaesser Heidi, Sauer Karsten, Brooks David G   IL-21 is required to control chronic viral infection Science (New York, N.Y.), 2009; 324(5934): 1569-72.
Wilson Elizabeth B, Brooks David G   Translating insights from persistent LCMV infection into anti-HIV immunity Immunologic research, 2010; 48(1-3): 3-13.
Fahey Laura M, Wilson Elizabeth B, Elsaesser Heidi, Fistonich Chris D, McGavern Dorian B, Brooks David G   Viral persistence redirects CD4 T cell differentiation toward T follicular helper cells The Journal of experimental medicine, 2011; 208(5): 987-99.
Fahey Laura M, Brooks David G   Opposing positive and negative regulation of T cell activity during viral persistence Current opinion in immunology, 2010; 22(3): 348-54.
Wilson Elizabeth B, Brooks David G   Inflammation makes T cells sensitive Immunity, 2013; 38(1): 5-7.
Wilson Elizabeth B, Yamada Douglas H, Elsaesser Heidi, Herskovitz Jonathan, Deng Jane, Cheng Genhong, Aronow Bruce J, Karp Christopher L, Brooks David G   Blockade of chronic type I interferon signaling to control persistent LCMV infection Science (New York, N.Y.), 2013; 340(6129): 202-7.
Kidani Yoko, Elsaesser Heidi, Hock M Benjamin, Vergnes Laurent, Williams Kevin J, Argus Joseph P, Marbois Beth N, Komisopoulou Evangelia, Wilson Elizabeth B, Osborne Timothy F, Graeber Thomas G, Reue Karen, Brooks David G, Bensinger Steven J   Sterol regulatory element-binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity Nature immunology, 2013; 14(5): 489-99.