tapping@life.illinois.edu
Office: (217) 244-7940
Lab: (217) 333-2203
Mail to:
B103 CLSL, MC-110
601 S. Goodwin Ave.
Urbana, IL 61801
Richard I Tapping
Associate Professor of Microbiology
Education
B.S. (Biochemistry), University of Waterloo, Canada, 1987
Ph.D. (Biochemistry), McMaster University, Canada, 1995
Postdoctoral (Immunology), Scripps Research Institute, 1995-1999
Senior Research Associate (Immunology), Scripps Research Institute, 1999-2002
Teaching Interests
The Role of Toll-like Receptors in Host Innate Immune Defense
The ability of host cells to sense and respond to non-self is dependent upon a number of secreted and cell-associated molecules of the innate immune system. In 1996, a receptor known as Toll was found to protect fruit flies from fungal infection by activating the production of antifungal peptides. Homologues of this receptor, called Toll-like receptors (TLRs), were subsequently uncovered in vertebrates and are the focus of our research.
Humans possess ten TLR family members subsets of which are expressed in epithelial cells, endothelial cells as well as leukocyte subtypes found in tissue and blood. TLRs are transmembrane receptors whose extracellular domain discriminates self from nonself through recognition of conserved structural components of viruses, bacteria, fungi, and protozoans. These include cell wall or membrane components of bacteria and fungi as well as modified nucleic acids of certain bacteria and viruses (see figure). Upon engaging a cognate microbial agonist, TLRs activate intracellular signals which induce the expression and cellular release of cytokines, chemokines and other mediators that facilitate local inflammation. Viral sensing TLRs trigger the production of Type I interferons which are essential for early antiviral defense. In addition to providing immediate protection for the host, the engagement of TLRs drives antigen presentation leading to the T and B cell responses associated with adaptive immunity. In this context, it is not surprising that inappropriate TLR activation is directly associated with a variety of inflammatory disorders ranging from sepsis, atherosclerosis, asthma, and certain autoimmune disorders.
Research in our lab is currently focused on understanding the evolution and biologic function of the TLR2 subfamily. TLR2 is unique among mammalian TLRs in that is requires heterodimeric association with other related TLR family members, which includes TLR1 or TLR6, in order to function. This flexibility enables this subfamily to respond to a wide variety of microbial and fungal components including cell wall components of Mycobacteria tuberculosis and Mycobacteria leprae.
With respect to the TLR2 subfamily, specific projects in the lab aim to:
- Identify novel agonists and define mechanisms of microbial recognition.
- Determine the subcellular trafficking patterns and signaling locations.
- Uncover the mechanisms by which gene expression is regulated.
- Determine mechanisms by which pathogens appear to have subverted this system.
- Identify and characterize functionally important genetic variants, especially in relation to human susceptibility to mycobacterial-associated diseases.
Within this framework, our lab utilizes a combination of biochemistry, molecular biology, cellular biology, and human population genetics techniques involving purified components, experimentally manipulated cell lines, blood cells, and TLR deficient mouse models. Research in our laboratory attempts to address the core question of how the innate immune system ultimately senses the presence of infection, identifies the type of invading pathogen, and mediates the appropriate response. This question is central to understanding basic immune defense as well as the pathogenesis of a wide variety of deleterious immune conditions.
Representative Publications
Tapping, R.I., Omueti, K.O., and Johnson, C.M. 2007. Genetic polymorphisms within the human Toll-like receptor 2-subfamily. Biochem. Soc. Trans., 35(6):1445-8.
Johnson, C.M. and Tapping, R.I. 2007. TLR2 expression is induced through chromatin remodeling around a proximal NF-kB element. J Biol Chem., 282(43):31197-205.
Schumann, R.R. and Tapping. R.I. 2007. Genomic variants of TLR1-It takes two to tango. Eur. J. Immunol., 37(8):2059-62. [Abstract]
Johnson, C.M., Lyle, E.A., Omueti, K.O., Stepensky V.A., and Tapping, R.I. 2007. Cutting Edge: A common single nucleotide polymorphism impairs surface trafficking and functional responses of Toll-like receptor 1 but protects against leprosy. J. Immunol., 178(12):7520-4. [Abstract]
Omueti, K.O., Muzar, D.J., Thompson, K.S., Lyle, E.A., and Tapping, R.I. 2007. The polymorphism P315L of Toll-like receptor 1 impairs innate immune sensing of microbial cell wall components. J. Immunol., 178 (10):6387-94. [Abstract]
Liang, S., Wang, M., Tapping, R.I., Stepensky, V., Nawar, H.F., Triantafilou, M., Triantafilou, K., Connell, T.D., and Hajishengallis, G. 2007. Ganglioside GD1a is an essential coreceptor for Toll-like receptor 2 signaling in response to the B subunit of type IIB enterotoxin. J Biol Chem., 282(10):7532-42. [Abstract]
Hajishengallis, G., Tapping, R.I., Harokopakis, E., Nishiyama, S., Ratti, P., Schifferle, R.E., Lyle, E.A., Trianafilou, M., Triantafilou, K., and Yoshimura, F. 2006. Differential interactions of fimbriae and lipopolysaccharide from Porphymonas gingivalis with the Toll-like receptor 2-centered recognition apparatus. Cell. Microbiol., 8(10):1557-70. [Abstract]
Omueti K.O., Beyer J.M., Johnson C.M., Lyle E.A., and Tapping R.I. 2005. Domain exchange between human toll-like receptors 1 and 6 reveals a region required for lipopeptide discrimination. J Biol Chem 280:36616–25. Epub 2005 Aug 29. [Abstract]
Hajishengallis, G., Tapping, R.I., Martin, M.H., Nawar, H., Lyle, E.A., Russell, M.W., and Connell, T.D. 2005. Toll-like receptor 2 mediates cellular activation by the B subunits of type II heat-labile enterotoxins. Infect. & Immun, 73:1343–9. [Abstract]
Vinogradov, E., Paul, C.J., Li, J., Zhou, Y., Lyle, E.A., Tapping, R.I., Kropinski, A.M., and Perry, M.B. 2004. The structure and biological character of the Spirochaeta aurantia outer membrane glycolipid. LGL B. Eur. J. Biochem, 271:4685–95. [Abstract]
Hajishengallis G., Newar, H., Tapping, RI., Russell, M.W., and Connell, T.D. 2004. Cytokine induction and regulation by the Type II heat-labile enterotoxins in human monocytic cells. Infect. & Immun, 72:6351–8. [Abstract]
Lee, J.Y., Zhao, L., Youn, H.S., Weatherill, A.R., Tapping, R., Feng, L., Lee, W.H., Fitzgerald, K.A., and Hwang, D.H. 2004. Saturated fatty acid activates but polyunsaturated fatty acid inhibits toll-like receptor 2 dimerized with toll-like receptor 6 or 1. J. Biol. Chem, 279:16971–9. [Abstract]
Tapping, R.I. and Tobias, P.S. 2002. Mycobacterial lipoarabinomannan mediates physical interactions between TLR1 and TLR2 to induce signaling. J. Endotoxin Res, 9:264–8. Abstract]
Werts, C., Tapping, R.I., Mathison, J.C., Chuang, T.H., Kravchenko, V., Saint Girons, I., Haake, D.A., Godowski, P.J., Hayashi, F., Ozinsky, A., Underhill, D.M., Kirschning, C.J., Wagner, H., Aderem, A., Tobias, P.S., and Ulevitch, R.J. 2001. Leptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism. Nature Immunol, 2(4):346–52. [Abstract]
Tapping, R.I., Akashi, S., Miyake, K., Godowski, P.J., and Tobias, P.S. 2000. Toll-like receptor 4, but not toll-like receptor 2, is a signaling receptor for Salmonella and Escherichia Lipopolysaccharides. J. Immunol, 165:5780–7. [Abstract]
Tapping, R.I. and Tobias, P.S. 2000. Soluble CD14 mediated cellular responses to Lipopolysacchride. Chem. Immunol, 74:108–21. [Abstract]
Tobias, P.S., Lee, H., Orr, S., Soldau, K., and Tapping, R.I. 2000. Innate immune system recognition of microbial pathogens. Immunol. Res, 21(2-3): 341–3. [Abstract]