Many epidemiological studies have suggested that the recent increase in prevalence and severity of allergic diseases such as
asthma is inversely correlated with Mycobacterium bovis bacillus Calmette Guerin (BCG) vaccination. However, the underlying mechanisms by which mycobacterial components suppress allergic diseases are not yet fully understood. Here we showed the inhibitory mechanisms for development of allergic airway
inflammation by using highly purified recombinant Ag85B (rAg85B), which is one of the major
protein antigens secreted from M.
tuberculosis. Ag85B is thought to be a single immunogenic
protein that can elicit a strong Th1-type immune response in hosts infected with mycobacteria, including individuals vaccinated with BCG. Administration of rAg85B showed a strong inhibitory effect on the development of allergic airway
inflammation with induction of Th1-response and IL-17and
IL-22 production. Both
cytokines induced by rAg85B were involved in the induction of Th17-related
cytokine-production innate immune cells in the lung. Administration of
neutralizing antibodies to
IL-17 or
IL-22 in rAg85B-treated mice revealed that
IL-17 induced the infiltration of neutrophils in BAL fluid and that
allergen-induced bronchial
eosinophilia was inhibited by
IL-22. Furthermore, enhancement of the expression of genes associated with tissue homeostasis and wound healing was observed in bronchial tissues after rAg85B administration in a Th17-related
cytokine dependent manner. The results of this study provide evidence for the potential usefulness of rAg85B as a novel approach for
anti-allergic effect and tissue repair other than the role as a conventional TB
vaccine.