Microbiology, Immunology & Molecular Genetics Faculty
Michael T. Berton, Ph.D.
Dr. Berton has a broad background in cellular and molecular immunology, molecular biology, and the study of infectious diseases. He also has extensive expertise in the areas of cytokine signaling and Toll-like receptor signaling. Dr. Berton completed his graduate and post-doctoral training in the laboratories of two National Academy of Sciences members, Dr. Robert G. Webster and Dr. Ellen S. Vitetta, where he made significant contributions to the fields of influenza genetics and B cell heavy chain class switching, respectfully. Early in his independent career, Dr. Berton studied the regulation of immunoglobulin heavy chain gene expression and class switching in B lymphocyctes. His lab made early contributions to understanding how IL-4-activated STAT6 and CD40L-CD40 interactions regulate germilne immunoglobulin heavy chain gene transcription and heavy chain class switching. In 2002, Dr. Berton began to also study Toll-like receptor signaling during immune responses to infection. His lab has now developed important collaborative partners, published several papers in this area, and made exciting novel findings that are now poised to pursue.
Ph.D., University of Tennessee center for the Health Sciences, Memphis, TN
Keywords: Cytokine and Toll-like receptor signaling; immunity to infection; Francisella tularensis
Dr. Berton's laboratory is interested in the molecular and cell biology of host cell signaling pathways that regulate innate and adaptive immune responses, and in the mechanisms that pathogens use to manipulate and evade host immunity. They are currently studying the role of Toll-like receptor (TLR) signaling in the immune response to the intracellular bacterial pathogen, Francisella tularensis. F. tularensis is a Gram-negative, facilitative, intracellular bacterial pathogen that causes the disease tularemia. F. tularensis type A and B strains have been classified as Tier 1 biodefense agents because of their high infectivity, extreme virulence, and ability to be disseminated by aerosol, yet there is no licensed vaccine for this highly virulent pathogen. A critical Francisella virulence trait is its ability to suppress the innate and adaptive immune responses, but little is known about the mechanisms underlying this suppression. The innate immune response to pathogens is initiated when the host is alerted to infection as a result of recognition of pathogen-derived molecules by pattern recognition receptors (PRRs), such as the Toll-like receptors (TLRs), that recognize and bind to conserved molecular motifs expressed by many pathogens. The TLRs are evolutionarily conserved, germline-encoded receptors that signal many cell types via a set of cytoplasmic signaling adapters that lead to MAP kinase and NF-κB activation. Binding of TLRs to pathogen-derived molecules induces the expression of chemokines and pro-inflammatory cytokines by many different cell types, and up-regulates the expression of MHC and co-stimulatory molecules on antigen-presenting cells required for the activation of T cells. Current studies in the lab are focused on identifying the role that TLR signaling plays in the host protective response against F. tularensis infection and on the mechanisms used by F. tularensis to evade or suppress those responses in a mouse model of pulmonary tularemia. Their expectation is that these studies will identify critical immune signaling pathways and mechanisms of immune evasion that must be considered in the development of a safe and effective F. tularensis vaccine.
Awards & Accomplishments
2004, Executive Research Committee Incentive Award, UTHSCSA
2012, Laboratory Travel Award from the American Association of Immunologists
Professional AffiliationsMember, American Association of Immunologists
Rodriguez AR, Yu JJ, Murthy AK, Guentzel MN, Navara, CS, Klose KE, Forsthuber TG, Chambers JP, Berton MT, Arulanandam BP. Mast cell toll-like receptor 2 signaling is crucial for effective killing of Francisella tularensis. J. Immunol. In Press, 2012.
Medina, E. A., I. R. Morris, and M. T. Berton. PI3-kinase activation attenuates the TLR2-mediated macrophage proinflammatory cytokine response to Francisella tularensis LVS infection. J. Immunol. 185:7562-7572, 2010.
Rodriguez A.R., Yu J.J., Murthy A.K., Guentzel M.N., Klose K.E., Forsthuber T.G., Chambers J.P., Berton M.T., Arulanandam B.P. Mast cell/IL-4 control of Francisella tularensis replication and host cell death is associated with increased ATP production and phagosomal acidification. Mucosal Immunol. ePub September 2010.
Abplanalp, A. L., I. R. Morris, B. K. Parida, J. M. Teale, and M. T. Berton. TLR–dependent control of Francisella tularensis infection and host inflammatory responses. PLoS ONE 4:e7920, 2009.
Berton M.T., L.A. Linehan, K.R. Wick and W.A. Dunnick. NF-κB elements associated with the Stat6 site in the germline γ1 immunoglobulin promoter are not necessary for the transcriptional response to CD40 ligand. Int. Immunol. 16:1741-1749, 2004.
Wick, K.R. and M.T. Berton. IL-4 induces serine phosphorylation of the STAT6 transactivation domain in B lymphocytes. Mol. Immunol. 37:641-652, 2000.
Harris, M.B., C.-C. Chang, M.T. Berton, N.N. Danial, J. Zhang, D. Kuehner, B.H. Ye, M. Kvatyuk, P.P. Pandolfi, G. Cattoretti, R. Dalla-Favera and P.B. Rothman. Transcriptional repression of Stat6-dependent interleukin-4-induced genes by BCL-6: specific regulation of Iε transcription and immunoglobulin E switching. Mol. Cell. Biol. 19:7264-7275, 1999.
Warren, W.D., K.L. Roberts, L.A. Linehan and M.T. Berton. Regulation of the germline immunoglobulin Cγ1 promoter by CD40L and IL-4: dual role for tandem NF-κB binding sites. Mol. Immunol. 36:31-44, 1999.
Linehan, L.A., W.D. Warren, P.A. Thompson, M.J. Grusby and M.T. Berton. STAT6 is required for IL-4-induced germline Ig gene transcription and switch recombination. J. Immunol. 161:302-310, 1998.