The overall goal of this project is to utilize the Mycoplasma arthritidis mitogen (MAM), a model superantigen, (SAg) to define how these substances influence the immune systems of their natural hosts, how they contribute to disease by the organisms that produce them and finally how they interact with compromised hosts leading to immune- mediated or autoimmune disease. Using homogeneous native MAM and/or rMAM-his the investigators will: 1. Define the in vivo effect of MAM on the normal murine host in respect to comparison of different mouse strains; identification of responding cell types; determine the requirements for immunoenhancement vs. immunosuppression; examine the effect of chronic exposure of mice to MAM and neutralization of the in vivo effects of MAM by passive or active immunization. 2. Elucidate the role of MAM in disease induced by M. arthritidis in respect to understanding the mechanisms of lethal toxic shock syndrome and necrotizing fasciitis, acute and chronic arthritis including the role of cytokines specifically produced by MAM or constitutively as a result of host genes; protection against the pathological effects due to MAM by administration of a mutant MAM vaccine and determination of the role played by the potential synergistic effects of MAM and other biologically-active components of M. arthritidis. 3. Determine the mechanisms by which MAM influences the development of autoimmunity by use of collagen-induced arthritis of mice and experimental allergic encephalomyelitis. Specifically the investigator shall define the role played by SAg-induced cytokines and protection against disease using the MAM vaccines described earlier.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Ridge, John P
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Utah
Internal Medicine/Medicine
Schools of Medicine
Salt Lake City
United States
Zip Code
Mu, Hong-Hua; Humphreys, Jennifer; Chan, Fok Vun et al. (2006) TLR2 and TLR4 differentially regulate B7-1 resulting in distinct cytokine responses to the mycoplasma superantigen MAM as well as to disease induced by Mycoplasma arthritidis. Cell Microbiol 8:414-26
Mu, H-H; Pennock, N D; Humphreys, J et al. (2005) Engagement of Toll-like receptors by mycoplasmal superantigen: downregulation of TLR2 by MAM/TLR4 interaction. Cell Microbiol 7:789-97
Mu, H H; Sawitzke, A D; Cole, B C (2001) Presence of Lps(d) mutation influences cytokine regulation in vivo by the Mycoplasma arthritidis mitogen superantigen and lethal toxicity in mice infected with M. arthritidis. Infect Immun 69:3837-44
Mu, H H; Sawitzke, A D; Cole, B C (2000) Modulation of cytokine profiles by the Mycoplasma superantigen Mycoplasma arthritidis mitogen parallels susceptibility to arthritis induced by M. arthritidis. Infect Immun 68:1142-9
Cole, B C (1999) Mycoplasma-induced arthritis in animals: relevance to understanding the etiologies of the human rheumatic diseases. Rev Rhum Engl Ed 66:45S-49S
Cole, B C; Sawitzke, A D; Ahmed, E A et al. (1997) Allelic polymorphisms at the H-2A and HLA-DQ loci influence the response of murine lymphocytes to the Mycoplasma arthritidis superantigen MAM. Infect Immun 65:4190-8
Knudtson, K L; Manohar, M; Joyner, D E et al. (1997) Expression of the superantigen Mycoplasma arthritidis mitogen in Escherichia coli and characterization of the recombinant protein. Infect Immun 65:4965-71
Cole, B C; Knudtson, K L; Oliphant, A et al. (1996) The sequence of the Mycoplasma arthritidis superantigen, MAM: identification of functional domains and comparison with microbial superantigens and plant lectin mitogens. J Exp Med 183:1105-10
Atkin, C L; Wei, S; Cole, B C (1994) The Mycoplasma arthritidis superantigen MAM: purification and identification of an active peptide. Infect Immun 62:5367-75
Griffiths, M M; Cole, B C; Ito, J et al. (1993) T-cell receptors and collagen induced arthritis in H-2r mice. Autoimmunity 14:221-9

Showing the most recent 10 out of 24 publications