(Verbatim from application) Dentoalveolar abscess causing bacteria evade ingestion and destruction by phagocytic leukocytes and other local host immune mechanisms. If not promptly treated, these infections may rapidly spread along fascial planes, through lymphatics and via the bloodstream, resulting in significant morbidity and even mortality. Individuals with immunodeficiencies, or undergoing chemotherapy or immunosuppression, are particularly vulnerable. During the first grant period we developed a novel mouse model in which T and B cell deficient (SCID) mice with mixed anaerobic pulpal infections develop dentoalveolar abscesses, disseminating infections and sepsis. B cell deficient mice were also susceptible but with reduced frequence, whereas T cell deficient mice were resistant. Dissemination was partially prevented by passive transfer of antibody. In this application we will elucidate the mechanisms that govern protection vs susceptibility to these infections.
In Aim 1, the bacterial complexes that can cause disseminating infections in this model will be characterized.
Aim 2 will determine the mechanism(s) of antibody - and phagocytic leukocyte-mediated protection against pathogens.
In Aim 3, the mechanism(s) of increased susceptibility to disseminating infections and septic shock in SCID vs B cell deficient mice will be determined. The role of T cells and chemotactic cytokines in protection, or NK cells and shock-associated cytokines in increasing susceptibility will be determined in vivo. The goal of these studies is to fully define the immunological effector mechanisms that protect against disseminating dentoalveolar infections

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE011664-07
Application #
6628417
Study Section
Special Emphasis Panel (ZRG1-GRM (04))
Program Officer
Bhargava, Sangeeta
Project Start
1996-02-01
Project End
2005-01-31
Budget Start
2003-02-01
Budget End
2004-01-31
Support Year
7
Fiscal Year
2003
Total Cost
$358,794
Indirect Cost
Name
Forsyth Institute
Department
Type
DUNS #
062190616
City
Boston
State
MA
Country
United States
Zip Code
02142
Youssef, Hesham; Stashenko, Philip (2017) Interleukin-1 and estrogen protect against disseminating dentoalveolar infections. Int J Oral Sci 9:16-23
Foschi, F; Izard, J; Sasaki, H et al. (2006) Treponema denticola in disseminating endodontic infections. J Dent Res 85:761-5
Foschi, F; Cavrini, F; Montebugnoli, L et al. (2005) Detection of bacteria in endodontic samples by polymerase chain reaction assays and association with defined clinical signs in Italian patients. Oral Microbiol Immunol 20:289-95
Dayan, S; Stashenko, P; Niederman, R et al. (2004) Oral epithelial overexpression of IL-1alpha causes periodontal disease. J Dent Res 83:786-90
Castro, G F; Souza, I P R; Lopes, S et al. (2004) Salivary IgA to cariogenic bacteria in HIV-positive children and its correlation with caries prevalence and levels of cariogenic microorganisms. Oral Microbiol Immunol 19:281-8
von Stechow, Dietrich; Balto, Khaled; Stashenko, Philip et al. (2003) Three-dimensional quantitation of periradicular bone destruction by micro-computed tomography. J Endod 29:252-6
Balto, Khaled; White, Robert; Mueller, Ralph et al. (2002) A mouse model of inflammatory root resorption induced by pulpal infection. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 93:461-8
Niederman, Richard; Kelderman, Hans; Socransky, Sigmund et al. (2002) Enhanced neutrophil emigration and Porphyromonas gingivalis reduction following PGG-glucan treatment of mice. Arch Oral Biol 47:613-8
Balto, K; Sasaki, H; Stashenko, P (2001) Interleukin-6 deficiency increases inflammatory bone destruction. Infect Immun 69:744-50
Niederman, R; Westernoff, T; Lee, C et al. (2001) Infection-mediated early-onset periodontal disease in P/E-selectin-deficient mice. J Clin Periodontol 28:569-75

Showing the most recent 10 out of 18 publications