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.
- Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Graduate Medical Sciences
- Professor, Microbiology, Boston University School of Medicine
- Active Staff Privileges, Infectious Diseases, Medicine, Boston Medical Center
- Harvard University, MD
- Holy Cross College, BA
- GMS MI823
- Med MS 220
- Published on 1/3/2018
Ray TD, Mekasha S, Liang Y, Lu B, Ram S, Ingalls RR. Species-specific differences in regulation of macrophage inflammation by the C3a-C3a receptor axis. Innate Immun. 2018 01; 24(1):66-78. PMID: 29297237.
- Published on 1/1/2018
Dutta Ray T, Mekasha S, Liang Y, Lu B, Ram S, Ingalls RR. Editor's Choice. Innate Immun. 2018 Jan; 24(1):3. PMID: 29313794.
- Published on 4/23/2017
Kramer CD, Simas AM, He X, Ingalls RR, Weinberg EO, Genco CA. Distinct roles for dietary lipids and Porphyromonas gingivalis infection on atherosclerosis progression and the gut microbiota. Anaerobe. 2017 Jun; 45:19-30. PMID: 28442421.
- Published on 2/9/2017
Aqeel Y, Rodriguez R, Chatterjee A, Ingalls RR, Samuelson J. Killing of diverse eye pathogens (Acanthamoeba spp., Fusarium solani, and Chlamydia trachomatis) with alcohols. PLoS Negl Trop Dis. 2017 Feb; 11(2):e0005382. PMID: 28182670.
- Published on 7/31/2016
Shaik-Dasthagirisaheb YB, Mekasha S, He X, Gibson FC, Ingalls RR. Signaling events in pathogen-induced macrophage foam cell formation. Pathog Dis. 2016 08; 74(6). PMID: 27481727.
- Published on 7/26/2016
Pudney J, He X, Masheeb Z, Kindelberger DW, Kuohung W, Ingalls RR. Differential expression of toll-like receptors in the human placenta across early gestation. Placenta. 2016 Oct; 46:1-10. PMID: 27697215.
- Published on 10/23/2015
He X, Liang Y, LaValley MP, Lai J, Ingalls RR. Comparative analysis of the growth and biological activity of a respiratory and atheroma isolate of Chlamydia pneumoniae reveals strain-dependent differences in inflammatory activity and innate immune evasion. BMC Microbiol. 2015; 15:228. PMID: 26494400.
- Published on 7/6/2015
Beaulieu LM, Clancy L, Tanriverdi K, Benjamin EJ, Kramer CD, Weinberg EO, He X, Mekasha S, Mick E, Ingalls RR, Genco CA, Freedman JE. Specific Inflammatory Stimuli Lead to Distinct Platelet Responses in Mice and Humans. PLoS One. 2015; 10(7):e0131688. PMID: 26148065.
- Published on 12/24/2014
Kramer CD, Weinberg EO, Gower AC, He X, Mekasha S, Slocum C, Beaulieu LM, Wetzler L, Alekseyev Y, Gibson FC, Freedman JE, Ingalls RR, Genco CA. Distinct gene signatures in aortic tissue from ApoE-/- mice exposed to pathogens or Western diet. BMC Genomics. 2014; 15:1176. PMID: 25540039.
- Published on 10/1/2014
Islam A, Marathe JG, Pudney J, Ayehunie S, Ingalls RR, Anderson DJ. Effects of endogenous and exogenous female reproductive hormones on gene expression and barrier function in female genital epithelia. AIDS Res Hum Retroviruses. 2014 Oct; 30 Suppl 1:A228. PMID: 25357642.
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