The major emphasis of work proposed in this project will continue to be directed toward an increased understanding of immune responses relevant to protection against chlamydial disease and defining how various elements of immunity to chlamydia contribute to protection, persistence, pathologic charges and recovery from infection. Much of the proposed work will involve studying of a murine model of protective immunity to chlamydia, recovery from chlamydial disease and persistence subsequent to either immunization or infection. Critical parameters related to cytokine mediated events also will be tested in vitro using human cell lines and, when appropriate, cytokines to evaluate if information obtained in the murine system applies to the human condition as well. The role of cytokines in mediating persistence, recovery from acute disease and cytolytic activity directed at infected host cells will be further evaluated. Renewed emphasis also will be placed on determining the extent of persistence subsequent to acute disease or induction of protective immunity following inoculation of viable chlamydial inocula. Cellular cloning of lymphocytes coupled with passive transfer experiments will provide evidence concerning the functional requirements for protective immunity and the chlamydial antigens that trigger induction of critical lymphocyte subpopulations. Innate defense will be compared between mouse strains that have recently been identified as differing in their susceptibility to chlamydia by approximately 100 million lethal inoculum doses. Finally, cross-protection studies will help elucidate the degree of immunity conferred between strains that differ to various extents in their antigenic composition.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI019782-07
Application #
3129196
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1982-08-01
Project End
1994-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
7
Fiscal Year
1991
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
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
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
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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