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| Innate Immune Recognition and Defense | |||||||
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Defense of all multi-cellular organisms from invading microbes depends on evolutionarily conserved systems that recognize and respond to highly conserved and unique microbial structures. The innate immune systems of the host include a broad array of proteins that together couple microbial recognition to activation of inflammation, killing and elimination of microbes and their remnants, and return of the host to a normal resting state. Our work concerns: 1) the molecular basis of microbial recognition by specific human innate defense proteins; 2) how this recognition is linked to specific cellular outcomes (e.g. activation (or de-activation) of host cells, elimination of viable microbes and their remnants); and 3) how the mobilization and function of these host proteins are regulated to permit an appropriate evolution of host responses to infection.
In addition, we make use of the experimental setting of bacterial attack by defined host defense proteins to study the molecular bases of bacterial stress responses to sub-lethal injury and, in particular, repair of membrane damage. We hope these studies will provide new insights on the maintenance and regulation of (bacterial) membrane homeostasis and identify new targets for antibiotic development. |
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| Selected Publications | |||||||
| Click Here for a Complete List of Articles | |||||||
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Trompette, A., Divanovic, S., Visintin, A., Blanchard, C., Hegde, R.S., Madan, R., Thorne, P.S., Wills-Karp, M., Gioannini, T.L., Weiss J.P. and Karp, C.L. Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein. Nature 457:585-588, 2009.
Resman, N., Vasl, J., Oblak, A., Pristovsek, P., Gioannini, T.L., Weiss J.P. and Jerala, R. Essential roles of hydrophobic residues in both MD-2 and Toll-like receptor 4 in activation of TLR4 by endotoxin. J. Biol. Chem. [Epub ahead of print] 284:15052-15060, 2009. Teghanemt, A., Widstrom, R.L., Gioannini, T.L. and Weiss J.P. Isolation of monomeric and dimeric secreted MD-2. Endtotoxin.sCD14 and Toll-like receptor 4 ectodomain selectively react with the monomeric form of secreted MD-2. J. Biol. Chem. 283:21881-9, 2008. PMC Journal - In Process. Koprivnjak, T., Weidenmaier, C., Peschel, A. and Weiss J.P. Wall teichoic acid deficiency in Staphylococcus aureus confers selective resistance to mammalian group IIA phospholipase A2 and human β defensin-3. Infect. Immun. 76:2169-2176, 2008. Schwartz, J., Leidal, K.G., Femling, J.K., Weiss J.P. and Nauseef, W.M. Neutrophil bleaching of GFP-expressing Staphylococci: probing the intraphagosomal fate of individual bacteria. J. Immunol. 183:2632-2641, 2009. Schultz, H., Hume, J., Zhang, D.S., Gioannini, T.L. and Weiss J. A novel role for the bactericidal/permeability-increasing protein (BPI) in interactions of Gram-negative bacteria outer membrane blebs with dendritic cells. J. Immunol. 179:2477-84, 2007. |
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| Department/Program Affiliations |
| Internal Medicine |
| Biosciences |
| Immunology |
| Microbiology |
| MSTP |