Dr. McGavern received his B.S degree in microbiology from The Pennsylvania State University and his Ph.D. in molecular neuroscience from the Mayo Clinic. Following an academic appointment as an Associate Professor in the Department of Immunology and Microbial Sciences at The Scripps Research Institute, Dr. McGavern joined the NINDS in March 2009. Dr. McGavern is the recipient of the prestigious Ray Thomas Edwards Foundation Award and the Burroughs Wellcome Fund Pathogenesis of Infectious Disease Award. His laboratory at the NIH is focused on states of acute and persistent infection of the central nervous system (CNS) as well as traumatic brain injury (TBI). As Chief of the Viral Immunology and Intravital Imaging Section, Dr. McGavern investigates how the innate and adaptive immune systems participate in different neurological disorders such as meningitis, encephalitis, cerebral malaria, and TBI.
My laboratory focuses on innate and adaptive immune responses to acute and persistent infection of the central nervous system (CNS) as well as sterile immune responses that develop following mild traumatic brain injury. The CNS is an immunologically specialized tissue containing a population of nonreplicative cells (neurons) responsible for a symphony of electrochemical signaling. The communication between neurons is exceedingly complex and contributes to nearly every aspect of our day-to-day functions. The immune system is equally complex (possessing both innate and adaptive components) and is assigned to the tasks of warding off microbes that invade all parts of the body as well as dealing with damaged tissues. For this reason, the immune system is highly mobile and equipped with effector mechanisms that neutralize pathogens and also molecules that facilitate tissue repair. Despite this balance, immune cells sometimes employ mechanisms that further damage tissues following infection or injury. From an immunological perspective, the CNS is an interesting compartment because it must preserve neuronal function while still enabling immune cells to survey the environment for pathogens and injury. The CNS and immune systems communicate with one another during states of health and disease, and it is the unique dialogue between two systems that guides much of our research. We focus specifically on immune cell surveillance of the infected CNS, pathogenesis of viral meningitis (a disease of the CNS lining), viral encephalitis, mechanisms that give rise to viral persistence, therapeutic approaches to purge infections, the pathogenesis of cerebral malaria (a disease caused by the parasite Plasmodium berghei), and immune reactions to traumatic brain injury. We use many contemporary approaches to gain novel insights into these research areas, the most exciting of which is intravital two-photon microscopy. This approach allows us to watch immune cells clear pathogens, cause diseases, or repair damaged tissues in real-time. Overall, our laboratory crosses the disciplines of virology/microbiology, immunology, and neuroscience in order to provide a comprehensive understanding of the different scenarios that unfold when the CNS is invaded by pathogens or is damaged by injury.
Choi, B., Johnson, K.R., Maric, D., and McGavern, D.B. Monocyte-derived IL-6 Programs Microglia to Rebuild Damaged Brain Vasculature. Nat Immunol. 24(7):1110-1123, 2023.
Mason H., Rai G., Kozyr A., De Jonge N., Gliniewicz E., Berg L.J., Wald G., Dorrier C., Henderson M.J., Zakharov A., Dyson T., Audley J., Pettinato A.M., Padilha E.C., Shah P., Xu X., Leto T.L., Simeonov A., Zarember K.A., McGavern D.B., and Gallin J.I. Development of an improved and specific inhibitor of NADPH oxidase 2 to treat traumatic brain injury. Redox Biol. 60:102611, 2023.
Mason, H.D., and McGavern, D.B. How the immune system shapes neurodegenerative diseases. Trends in Neurosci. 45(10):733-748, 2022.
Ampie, L., and McGavern, D.B. Immunological defense of central nervous system barriers against infections. Immunity. 55(5):781-799, 2022.
Dorrier, C.E., and McGavern, D.B. Humoral immune defense of the central nervous system. Curr Opin Immunol. 76:102179, 2022.
Buckley, M.W., and McGavern, D.B. Immune dynamics in the CNS and its barriers during homeostasis and disease. Immunol Rev. 306(1):58-75, 2022.
Zhang Y., Bailey J.T., Xu E., Singh K., Lavaert M., Link V.M., D'Souza S., Hafiz A., Cao J., Cao G., Sant'Angelo D.B., Sun W., Belkaid Y., Bhandoola A., McGavern D.B., and Yang Q. Mucosal-associated invariant T cells restrict reactive oxidative damage and preserve meningeal barrier integrity and cognitive function. Nat Immunol. 23(12):1714-1725, 2022.
Rebejac J., Eme-Scolan E., Arnaud Paroutaud L., Kharbouche S., Teleman M., Spinelli L., Gallo E., Roussel-Queval A., Zarubica A., Sansoni A., Bardin Q., Hoest P., Michallet M.C., Brousse C., Crozat K., Manglani M., Liu Z., Ginhoux F., McGavern D.B., Dalod M., Malissen B., Lawrence T., and Rua R. Meningeal macrophages protect against viral neuroinfection. Immunity. 55(11):2103-2117, 2022
Mason, H.D., Johnson, A.M., Mihelson, N.A., Mastorakos, P., and McGavern, D.B. Glia limitans superficialis oxidation and breakdown promotes cortical cell death after repeat head injury. JCI Insight. 6(19):e149229, 2021.
Absinta M., Maric D., Gharagozloo M., Garton T., Smith M.D., Jin J., Fitzgerald K.C., Song A., Liu P., Lin J.P., Wu T., Johnson K.R., McGavern D.B., Schafer D.P., Calabresi P.A., and Reich D.S. A lymphocyte-microglia-astrocyte axis in chronic active multiple sclerosis. Nature. 597(7878):709-714, 2021.
Mastorakos, P., Mihelson, N., Luby, M., Burks, S.R., Johnson, K., Hsia, A.W., Witko, J., Frank, J.A., Latour, L., and McGavern, D.B. Temporally Distinct Myeloid Cell Reponses Mediate Damage and Repair After Cerebrovascular Injury. Nat Neurosci. 24(2):245-258, 2021.
Mihelson, N., and McGavern, D.B. Viral control of glioblastoma. Viruses. 13(7):1264, 2021.
Fitzpatrick, Z., Frazer, G., Ferro, A., Clare, S., Bouladoux, N., Ferdinand, J., Tuong, Z.K., Negro-Demontel, M.L., Suchanek,, O., Tajsic, T., Harcourt, K., Scott, K., Bashford-Rogers, R., Helmy, A., Reich, D.S., Belkaid, Y., Lawley, T., McGavern, D.B., and Clatworthy, M.R. Gut-educated IgA plasma cells form an immunological defense at meningeal venous sinuses. Nature. 587(7834):472-476, 2020.
Riggle, B.A., Manglani, M., Maric, D., Johnson, K.R., Lee, M., Neto, O.L., Taylor, T.E., Seydel, K.B., Milner, D.A., Nath, A., Miller, L.H., McGavern, D.B., and Pierce, S.K. CD8+ T cells target brain vasculature in children with cerebral malaria. J Clin Invest. 30(3):1128-1138, 2020.
Rua, R., Lee, J.Y., Silva, A.B., Swafford, I.S., Maric, D., Johnson K.R., and McGavern, D.B. Infection drives long-term meningeal engraftment by inflammatory monocytes that impair central nervous system immunity. Nat Immunol. 20(4):407-419, 2019.
Manglani, M., Gossa, S., and McGavern, D.B. Isolation of leukocytes from brain, spinal cord, and meninges for flow cytometric analysis. Curr Protoc Immunol. 121(1):e44, 2018.
Manglani, M., and McGavern, D.B. Intravital imaging of neuroimmune interactions through a thinned skull. Curr Protoc Immunol. 120: 24.2.1–24.2.12, 2018.
Russo, M.V., Latour, L.L., and McGavern, D.B. Distinct myeloid cell subsets promote meningeal vascular remodeling and repair following mild traumatic brain injury. Nat Immunol. 19(5):442-452, 2018.
Rua, R., and McGavern, D.B. Advances in meningeal immunity. Trends Mol Med. 24(6):542-559, 2018.
Manglani, M., and McGavern, D.B. New advances in CNS immunity against viral infection. Curr Opin Virol. 28:116-126, 2018.
Kwong, B., Rua, R., Gao, Y., Flickinger Jr., J., Wang, Y., Kruhlak, M.J., Zhu, J., Vivier, E., McGavern, D.B., and Lazarevic, V. T-bet-dependent NKp46+ innate lymphoid cells regulate the onset of TH17-induced neuroinflammation. Nat Immunol. 18(10):1117-1127, 2017.
Pandya, H., Shen, M.J.., Ichikawa, D.M., Sedlock, A.B., Choi, Y., Johnson, K.R., Kim, G., Brown, M.A., Elkahloun, A.G., Maric, D., Sweeney, C.L., Malech, H.L., McGavern, D.B., and Park, J.K. Differentiation of human and murine induced pluripotent stem cells to microglia-like cells. Nat Neurosci. 20(5):753-759, 2017.
Jassam, Y.N., Izzy, S., Whalen, M., McGavern, D.B., and El Khoury J. Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift. Neuron. 95(6):1246-1265, 2017.
Swanson, P.A., Hart, G.T., Russo, M.V., Nayak, D., Yazew, T., Peña, M., Khan, S.M., Janse, C.J., Pierce, S.K., and McGavern, D.B. CD8+ T cells induce fatal brainstem pathology during cerebral malaria via luminal antigen-specific engagement of brain vasculature. PloS Pathogens. 12(12):e1006022, 2016.
Moseman, E.A., Wu, T., de la Torre, J.C., Schwartzberg, P.L., and McGavern, D.B. Type I IFN suppresses virus-specific B cell responses by modulating CD8+ T cell differentiation. Sci Immunol. 1(4): eaah3565, 2016.
Russo, M., and McGavern, D.B. Inflammatory neuroprotection following traumatic brain injury. Science. 353(6301):783-5, 2016.
Konradt, C., Ueno, N., Christian, D.A., Delong, J.H., Harms-Pritchard, G., Herz, J., Bzik, D.J., Koshy, A.A., McGavern, D.B., Lodoen, M.B., and Hunter, C.A. Endothelial cells are a replicative niche for entry of Toxoplasma gondii to the central nervous system. Nat Microbiol. 1:1-8, 2016.
Herz, J., Johnson, K., and McGavern, D.B. Therapeutic antiviral T cells noncytopathically clear persistently infected microglia after conversion into antigen-presenting cells. J Exp Med. 212(8):1153-69, 2015.
Cardoso F.L., Herz J., Fernandes A., Rocha J., Sepodes B., Brito M.A., McGavern D.B., and Brites D. Systemic inflammation in early neonatal mice induces transient and lasting neurodegenerative effects. J Neuroinflammation. 12:82, 2015.
Russo, M., and McGavern, D.B. Immune surveillance of the CNS following infection and injury. Trends Immunol. 36(10):637-50, 2015.
Rua, R., and McGavern, D.B. Elucidation of monocyte / macrophage dynamics and function by intravital imaging. J Leukoc Biol. 98(3):319-32, 2015.
Swanson, P., and McGavern, D.B. Viral diseases of the central nervous system. Curr Opin Virol. 11C:44-54, 2015.
Corps, K.N., Roth, T.L., and McGavern, D.B. Inflammation and neuroprotection in the traumatically injured brain. JAMA Neurology. 72(3):355-62, 2015.
Roth, T.L., Nayak, D., Atanasijevic, T., Koretsky, A.P., Latour, L.L., and McGavern, D.B. Transcranial amelioration of inflammation and cell death following brain injury. Nature. 505(7482):223-8, 2014.
Nayak, D., Roth, T.L., and McGavern, D.B. Microglia development and function. Ann Rev Immunol. 32:367-402, 2014.
Nayak, D., Johnson, K., Heydari, S., Roth, T.L., Zinselmeyer, B.H., and McGavern, D.B. Type I interferon induces innate myeloid cell dynamics and gene expression during CNS viral infection. PloS Pathogens. 9(5):e1003395, 2013.
Zinselmeyer, B.H., Heydari, S., Nayak, D., and McGavern, D.B. PD-1 promotes immune exhaustion by inducing anti-viral T cell motility paralysis. J Exp Med. 210(4):757-74, 2013.
Moseman, E.A. and McGavern, D.B. The great balancing act: regulation and fate of antiviral T cell interactions. Immunol Rev. 255(1):110-24, 2013.
Nayak, D., Zinselmeyer, B.H., Corps, K.N., and McGavern, D.B. In vivo dynamics of innate immune sentinels in the CNS. IntraVital. 1(2): 95-106, 2012.
Herz, J., Zinselmeyer, B.H., and McGavern, D.B. Two-photon imaging of microbial immunity in living tissues. Microsc Microanal. 18: 730-741, 2012.
Fahey, L.M., Wilson, E.B., Elsaesser, H., McGavern, D.B., and Brooks, D.B. Viral persistence redirects CD4 T cell differentiation toward T follicular helper cells. J Exp Med. 208(5):987-99, 2011.
Kang, S.S., Herz, J., Kim, J.V., Nayak, D., Stewart-Hutchinson, P., Dustin, M.L. & McGavern, D.B. Migration of cytotoxic lymphocytes in cell cycle permits local MHC I-dependent control of division at sites of viral infection. J Exp Med. 208 (4): 747-759, 2011.
Kang, S.S., and McGavern, D.B. Illuminating viral infections of the nervous system. Nat Rev Immunol. 11(5): 318-29, 2011.
Truong, P., Heydari, S., Garidou, L., and McGavern, D.B. Persistent viral infection elevates CNS MHC I through chronic production of interferons. J Immunol. 183(6):3895-905, 2009.
Garidou, L., Heydari, S., Truong, P., Brooks, D.G., and McGavern, D.B. Therapeutic memory T cells require costimulation for effective clearance of a persistent viral infection. J Virol. 83(17):8905-15, 2009.
Kim, J.V., Kang, S.S., Dustin, M.L. and McGavern, D.B. Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis. Nature. 457(7226):191-5, 2009.
Kang, S., and McGavern, D.B. Inflammation on the mind: visualizing immunity in the central nervous system. Curr Top Microbiol Immunol. 334:227-63, 2009.
Lauterbach, H., Truong, P., and McGavern, D.B. Clearance of an immunosuppressive virus from the CNS coincides with immune reanimation and diversification. Virology J. 4:53, 2007.
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. Nat Med. 12(11):1301-1309, 2006.
Lauterbach, H., Zuniga, E.I., Truong, P., Oldstone, M.B.A., and McGavern, D.B. Adoptive immunotherapy induces CNS dendritic cell recruitment and antigen presentation during clearance of a persistent viral infection. J Exp Med. 203:1963-1975, 2006.
Brooks, D.G., Teyton, L., Oldstone, M.B.A., and McGavern, D.B. Intrinsic functional dysregulation of CD4 T cells occurs rapidly following persistent viral infection. J Virol. 79:10514-10527, 2005.