The purpose of the Animal Core of this Program Project is to support the four research projects by maintaining and breeding mice, collecting cells, tissues and blood from mice, performing bacterial infection with Porphyromonas gingivalis and Chlamydia pneumoniae, and performing in vivo imaging studies by MRI / MRA. To define cell specificity of IL-lp signaling in the development of inflammatory atherosclerotic plaque, the Animal Core will perform bone marrow transplantation to produce bone marrow chimeric mice in which either the donor cells or the recipient mice are IL-1p KO, and challenge these mice with C. pneumoniae or P. gingivalis. The Animal Core will generate two novel transgenic mice, in which TLR2 or IL-1 receptor (IL- 1R) expression is targeted specifically to endothelial cells. These mice will be used to examine endothelial cell TLR2 or IL-IR signaling in inflammatory responses to P. gingivalis and C. pneumoniae infection. We currently maintain some of these KO mice in our mouse colony, including the ApoE, TLR2, IL-1 R single KO mice as well as ApoE/TLR2 double KO mice. We will obtain IL-ip, LXRa, LXRp single KO mice, and LXRa/p double KO mice.We will cross KO mice to generate double KO mice: ApoE x LXRa, ApoE x LXRp, ApoE X IL-IR, and ApoE x IL-1 p. To support the four Projects of the Program, we propose the following Aims for the Animal Core:
AIM 1. Maintain and breed knockout mouse lines.
AIM 2. Obtain cell, tissue and blood samples from mice for analysis by each project.
AIM 3. Perform infection of P. gingivalis or C. pneumoniae, generate bone marrow chimeric mice by bone marrow transplantation, and perform MRI / MRA for each project.
AIM 4. Construct novel transgenic mice strains in which TLR2 or IL-IR expression is targeted to endothelial cells.

Public Health Relevance

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI078894-03
Application #
8380363
Study Section
Special Emphasis Panel (ZAI1-PRJ-I)
Project Start
Project End
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
3
Fiscal Year
2012
Total Cost
$301,402
Indirect Cost
$26,914
Name
Boston University
Department
Type
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Papadopoulos, G; Shaik-Dasthagirisaheb, Y B; Huang, N et al. (2017) Immunologic environment influences macrophage response to Porphyromonas gingivalis. Mol Oral Microbiol 32:250-261
Kramer, Carolyn D; Simas, Alexandra M; He, Xianbao et al. (2017) Distinct roles for dietary lipids and Porphyromonas gingivalis infection on atherosclerosis progression and the gut microbiota. Anaerobe 45:19-30
Shaik-Dasthagirisaheb, Yazdani B; Mekasha, Samrawit; He, Xianbao et al. (2016) Signaling events in pathogen-induced macrophage foam cell formation. Pathog Dis 74:
El-Awady, Ahmed R; Miles, Brodie; Scisci, Elizabeth et al. (2015) Porphyromonas gingivalis evasion of autophagy and intracellular killing by human myeloid dendritic cells involves DC-SIGN-TLR2 crosstalk. PLoS Pathog 10:e1004647
Koupenova, Milka; Mick, Eric; Mikhalev, Ekaterina et al. (2015) Sex differences in platelet toll-like receptors and their association with cardiovascular risk factors. Arterioscler Thromb Vasc Biol 35:1030-7
He, Xianbao; Liang, Yanmei; LaValley, Michael P et al. (2015) 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 15:228
Huang, N; Shaik-Dasthagirisaheb, Y B; LaValley, M P et al. (2015) Liver X receptors contribute to periodontal pathogen-elicited inflammation and oral bone loss. Mol Oral Microbiol 30:438-50
Beaulieu, Lea M; Clancy, Lauren; Tanriverdi, Kahraman et al. (2015) Specific Inflammatory Stimuli Lead to Distinct Platelet Responses in Mice and Humans. PLoS One 10:e0131688
Shaik-Dasthagirisaheb, Y B; Huang, N; Weinberg, E O et al. (2015) Aging and contribution of MyD88 and TRIF to expression of TLR pathway-associated genes following stimulation with Porphyromonas gingivalis. J Periodontal Res 50:89-102
Kramer, Carolyn D; Weinberg, Ellen O; Gower, Adam C et al. (2014) Distinct gene signatures in aortic tissue from ApoE-/- mice exposed to pathogens or Western diet. BMC Genomics 15:1176

Showing the most recent 10 out of 30 publications