Immunotherapy with mycobacteria.
OBJECTIVE
To summarize and evaluate critically recent progress with mycobacteria as a potential novel disease modifying treatment strategy in asthma.


RESULTS
The link between exposure to pathogenic or saprophytic mycobacteria and protection from allergic diseases is still controversial, and recent epidemiological studies, which addressed only exposure to Mycobacterium tuberculosis or bacillus Calmette-Guérin, did not help to clarify this issue. Moreover, the clear efficacy of mycobacterial treatment seen in animal models has not been reproduced in human asthma, and a recent small study testing the hypothesis that heat-killed Mycobacterium vaccae attenuates asthmatic reactions after allergen challenge did not provide convincing results. However, it has been shown that treatment of mice with M. vaccae induces the generation of allergen-specific T regulatory cells capable of suppressing allergen-mediated eosinophilic lung inflammation, suggesting that a general deficiency of T regulatory cell activity might be responsible for the increased prevalence of asthma. This hypothesis is supported by findings that a lack of T regulatory cells, as found in genetic disorders of man and mouse attributable to a mutation of Foxp3, a transcription factor specifically expressed by T regulatory cells, is associated with manifestations of severe atopy and autoimmunity, precisely the spectrum of diseases linked to the hygiene hypothesis.


CONCLUSIONS
Further studies on the relationship between mycobacteria and atopic disorders are needed, but there is reason to believe that the novel findings and molecular mechanisms associated with mycobacterial infections will further strengthen the currently unproved therapeutic value of immunotherapy with mycobacteria.
Walker
Christoph
C
Novartis Horsham Research Centre, Horsham, UK. christoph.walker@pharma.novartis.com
Sawicka
Elzbieta
E
Rook
Graham A W
GA
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001249:Asthma / Q000628:therapy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007167:Immunotherapy; D009161:Mycobacterium / Q000472:pathogenicity*; D009164:Mycobacterium Infections / Q000382:microbiology / Q000628:therapy*; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity
D000900:Anti-Bacterial Agents