The long term goal of the proposed research is to determine the role, if any, that IgA Fc receptors on the surface of bacteria play in the pathogenesis of respiratory disease. IgG Fc receptors, most notably Protein A, have been characterized and studied extensively. IgA Fc receptors are less well characterized, and to date have been described in Group A and B streptococci. We have identified several mycoplasmal species which bind human IGA Fc fragments. All of the mycoplasmal species which bound IgA Fc fragments were associated with respiratory disease in their natural host. A major deterrent to determination of the significance of IgA Fc receptors in disease has been the lack of a model system to adequately evaluate the impact of the Fc receptors on microbial pathogenicity. One of the IgA-binding mycoplasma species, Mycoplasma pulmonis, is the etiologic agent of murine respiratory mycoplasmosis (MRM), and is an excellent experimental model for infectious respiratory disease. We will characterize the IgA Fc receptors(s) on M. pulmonis with respect to specificity for immunoglobulin classes and subclasses from different host species. We will determine if mycoplasmas of human origin also express IgA Fc receptors. We will isolate and purify the IgA Fc receptors(s) on M. pulmonis, and determine the biochemical and immunochemical properties of the purified Fc receptor(s). The significance of IgA Fc receptor(s) in respiratory disease will be determined based on expression by strains on M. pulmonis which differ in virulence, expression of Fc receptor after passage in the natural host, and effects on pulmonary clearance after aerosol exposure to IgA-coated M. pulmonis. The character of potential IgAl and IgA2 Fc receptors could represent a potentially useful tool in elucidation of IgA Fc mediated effector functions. Finally, the presence of IgA Fc receptors on the surface of M. pulmonis coupled with the defined parameters for production and quantitation of respiratory disease in the mouse system make this a particularly attractive model to determine the impact of bacterial IgA Fc receptors on respiratory disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI029084-02
Application #
3455446
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1990-02-01
Project End
1995-01-31
Budget Start
1991-02-01
Budget End
1992-01-31
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Florida
Department
Type
Schools of Veterinary Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611