Robin Ingalls, M.D.
Professor of Medicine and Microbiology
650 Albany Street; X629
B.A. College of the Holy Cross
M.D. Harvard Medical School
The ability of innate immune system to sense invasion by a pathogenic organism and respond appropriately in order to control infection is paramount to survival. To that end, an array of receptors and binding proteins has evolved as part of the innate immune system to detect invading microorganisms. My laboratory is interested in Toll-like receptors and the intracellular signaling pathways that contribute to the innate recognition of Gram-negative bacteria, with a particular focus on mucosal immunity. We have a variety of in vitro and in vivo models in the laboratory to address the interaction of Neisseria and Chlamydia species with epithelial cells and macrophages.
One major focus of the laboratory is exploring the role of TLR2 in host defense against C. trachomatis. Previous work in our laboratory established a role for TLR2 in cellular responses to chlamydia species. In our recent in vivo work we have observed that TLR2 plays a protective role in the lung but a detrimental role in the genital tract during infected of mice with the mouse pathogen, C. muridarum. The goal of this project is to determine the specific cell types that are responsible for this difference. As part of this project, we are also trying to identify the specific ligands in chlamydia that are important for TLR2-dependent and independent cell activation, and characterize TLR2 signaling mutant strains of chlamydia that lack the cryptic plasmid.
A second focus of the laboratory is exploring the role TLRs and NLRs in host defense against N. gonorrhoeae. Previous work in our laboratory established a role for TLR4 and TLR2 in cellular responses to Neisseria species in vitro and we have recently completed in vitro studies that also demonstrate that gonorrhea can activate Nod receptors. Our ongoing in vivo studies in TLR4 mutant mice demonstrate that TLR4 is important for early bacterial clearance and neutrophil function, and we plan to complete studies in TLR2 and Nod1/2 mutant mice when back breeding is complete.
The third focus of the laboratory relates to the role of innate immunity on regulating acute and chronic inflammation associated with the respiratory pathogen Chlamydophila pneumoniae. We are in the process of defining the specific receptors and ligands that are responsible for IL-1b activation during infection, and will investigate the role of IL-1b in C. pneumoniae-induced atherosclerosis.
Packiam M., Wu H., Veit S.J., Mavrogiorgos N., Jerse A.E., and Ingalls R.R. 2012. Protective Role of Toll-like Receptor 4 in Experimental Gonococcal Infection of Female Mice. Mucosal Immunol. 5(1):19-29. PMID: 21937985
He X., Nair A., Mekasha S., Alroy J., O’Connell C.M., Ingalls R.R. 2011. Enhanced Virulence of Chlamydia muridarum Respiratory Infections in the Absence of TLR2 Activation. PLoS One 6(6): e20846. PMID: 21695078
He X., Mekasha S., Mavrogiorgos N., Fitzgerald K.A., Lien E., and Ingalls R.R. 2010. Inflammation and Fibrosis during Chlamydia pneumoniae Infection is Regulated by IL-1 and the NLRP3/ASC Inflammasome. J. Immunol. 184(10):5743-54. PMID: 20393140
Packiam M., Veit S.J., Anderson D.J., Ingalls R.R. and Jerse A.E. 2009. Mouse Strain-dependent Differences in Susceptibility to Neisseria gonorrhoeae Infection and Induction of Innate Immune Responses. Infect. Immun. 78(1):433-40. PMID: 19901062
O’Connell CM, Ingalls RR, Andrews CW Jr, Scurlock AM, Darville T. 2007. Plasmid-deficient Chlamydia muridarum fail to induce immune pathology and protect against oviduct disease. J Immunol. 179: 4027-34. [PMID: 17785841]
O’Connell, C.M., I.A. Ionova, A.J. Quayle, A. Visintin, and R.R. Ingalls. 2006. Localization of TLR2 and MyD88 to C. trachomatis inclusions: Evidence for signaling by intracellular TLR2 during infection with an obligate intracellular pathogen. J Biol Chem 281:1652-9. [PMID: 16293622]
Andersen, J.M.A., D. Al-Khairy, R.R. Ingalls. 2006. Innate immunity at the mucosal surface: role of toll-like receptor 3 and toll-like receptor 9 in cervical epithelial cell responses to microbial pathogens. Biol Reprod 74:824-31. [PMID: 16421230]
Fisette PL, S. Ram, J.M. Andersen, W. Guo, R.R. Ingalls. 2003. The lip lipoprotein from Neisseria gonorrhoeae stimulates cytokine release and NF-kB activation in epithelial cells in a TLR2-dependent manner. J Biol Chem 278:46252-60. [PMID: 12966099]
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