The aim of this project is to understand parameters associated with immunity against chlamydial infection and the response that occurs subsequent to immunization or infection. A murine-C. psittaci model will be employed for much of the proposed work. Special attention will be paid to distinguishing events that lead to protective immunity as opposed to immune-mediated latency. The latter phenomenon has been partially defined during the first 3 years of this project. Chlamydial latency will be studied in detail by completing the identification of the latency-inducing lymphokine, comparing in vitro induced latency with in vivo activated peritoneal cells and cryptically infected cells in culture. Mechanisms of latency will be investigated by establishing metabolic changes that accompany host cell activation and alterations of the metabolite pool that may lead to reversal of the active state. Comparisons will be made between gamma-interferon-like lymphokine activity and the known actions induced by interferons. Similarities and distinctions will be sought in lymphokine activity and antiviral mechanisms induced in interfron-treated cells. Immunity will be studied in comparative experiments involving active infections and immunizations using subcutaneous inoculation of viable chlamydiae, chlamydial cell envelope, and purified envelope components. Induction of IgM, IgG, and IgA will be measured by an indirect fluorescence test. Neutralizing antibody levels in serum and secretions will also be measured. Specific and non-specific blastogenesis, cytotoxic effector cell activity, antibody secretion via a plaque assay and lymphokine induction will be incorporated into all infection and immunization protocols. Evidence for immunosuppression will also be sought with the plaque assay to unrelated thymus dependent and independent antigens and also in the blastogenic assay. Results will help elucidate immune effector mechanisms against Chlamydia and distinguish protective from non-protective immunity. The long term goal of the investigation is to help establish if chlamydial vaccines are feasible, and if so, define the conditions that promote protective immunity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI019782-04
Application #
3129194
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1982-08-01
Project End
1988-12-31
Budget Start
1987-07-01
Budget End
1988-12-31
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Grayston, J Thomas; Belland, Robert J; Byrne, Gerald I et al. (2015) Infection with Chlamydia pneumoniae as a cause of coronary heart disease: the hypothesis is still untested. Pathog Dis 73:1-9
Peters, Jan; Byrne, Gerald I (2015) Chlamydia trachomatis growth depends on eukaryotic cholesterol esterification and is affected by Acyl-CoA:cholesterol acyltransferase inhibition. Pathog Dis 73:ftv028
Patil, Renukadevi; Szabó, Erzsébet; Fells, James I et al. (2015) Combined mitigation of the gastrointestinal and hematopoietic acute radiation syndromes by an LPA2 receptor-specific nonlipid agonist. Chem Biol 22:206-16
Bonner, Carol A; Byrne, Gerald I; Jensen, Roy A (2014) Chlamydia exploit the mammalian tryptophan-depletion defense strategy as a counter-defensive cue to trigger a survival state of persistence. Front Cell Infect Microbiol 4:17
Bavoil, Patrik M; Byrne, Gerald I (2014) Analysis of CPAF mutants: new functions, new questions (the ins and outs of a chlamydial protease). Pathog Dis 71:287-91
Abdelsamed, Hossam; Peters, Jan; Byrne, Gerald I (2013) Genetic variation in Chlamydia trachomatis and their hosts: impact on disease severity and tissue tropism. Future Microbiol 8:1129-1146
Jonsson, Colleen B; Cole, Kelly Stefano; Roy, Chad J et al. (2013) Challenges and Practices in Building and Implementing Biosafety and Biosecurity Programs to Enable Basic and Translational Research with Select Agents. J Bioterror Biodef Suppl 3:12634
Miyairi, Isao; Ziebarth, Jesse; Laxton, Jonathan D et al. (2012) Host genetics and Chlamydia disease: prediction and validation of disease severity mechanisms. PLoS One 7:e33781
Ziebarth, Jesse D; Bhattacharya, Anindya; Chen, Anlong et al. (2012) PolymiRTS Database 2.0: linking polymorphisms in microRNA target sites with human diseases and complex traits. Nucleic Acids Res 40:D216-21
Peters, Jan; Onguri, Vijaya; Nishimoto, Satoru K et al. (2012) The Chlamydia trachomatis CT149 protein exhibits esterase activity in vitro and catalyzes cholesteryl ester hydrolysis when expressed in HeLa cells. Microbes Infect 14:1196-204

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