A B-cell mitogen of Brucella abortus is an immmunomodulator

SPERA JM, COMERCI DJ, UGALDE JE, IÑON N, UGALDE RA

Pinamar, Buenos Aires, ARgentina

Congreso; SAIB XLI; 2005

One of the oustanding characteristics of brucellosis is the establishment of a chronic infection that can persist over the life span of the host. The isolation and characterization of moleculs that interact with the host immune defenses are fundamental for understanding the pathology and for the development of rationale strategies for vaccination, immunotherapy and drug design. B. abortus Rac1 is a 35kDa protein of the proline-racemase familty. These enzymes catalyze the interconvertion between L- and D-proline enantiomers and have been reported in Trypanosoma cruzi to act as B-cell polyclonal activatorIt has been demonstrated that mitogens and B-cell polyclonal activators are associated in many pathogenic microorganisms with immunemodulation and immunevasion. We describe that B.abortus Rac1 is a D-proline isomerase rather than a proline racemase. Integrity of the catalytic site is required for in vivo and in vitro B-cell mitogenic activity. During the acute phase of infection splenocyte of mice infected with wild type strain were unable to proliferate in response to ConA or LPS whereas those from mice infected with a rac1 mutant were competent to proliferate upon these stimulations. Moreover, persistance of rac1 mutant was severely affected in Balb/c mice experimental infections. All these results suggest that B. abortus RAC1 is a B-cell polyclonal activator and a strong immmunemodulator.