Application of heat killed Mycobacterium bovis-BCG into the lung inhibits the development of allergen-induced Th2 responses.
We have previously reported that an infection of the lung with BCG-inhibited ovalbumin (OVA)-induced airway eosinophilia. In the current study, we investigated if the intranasal application of heat killed (HK)-BCG or purified protein derivative (PPD) from Mycobacterium tuberculosis had the same effect. For this purpose we treated mice intranasally with either live BCG, HK-BCG or PPD and analyzed if the mice developed airway eosinophilia after immunization and intranasal challenge with OVA. Our results clearly showed that an intranasal vaccination with live and HK-BCG but not PPD, given 4 or 8 weeks prior to allergen airway challenge, resulted in a strong suppression of airway eosinophilia. The inhibition of airway eosinophilia correlated with reduced levels of IL-5 production by T cells from the lymph node of the lungs and a strong reduction in Th2 cell numbers present in the airways of OVA-challenged mice. Furthermore, HK-BCG-induced suppression of airway eosinophilia was strongly reduced in IFN-gamma deficient mice. HK-BCG in contrast to live BCG may also be a promising candidate for a prospective asthma vaccine in humans since negative side effects due to mycobacterial infection can be ruled out.
Major
Tamás
T
Centre for Infectious Diseases, University of Würzburg, Röntgenring 11, 97070 Würzburg, Germany.
Wohlleben
Gisela
G
Reibetanz
Birgit
B
Erb
Klaus Joseph
KJ
D000281:Administration, Intranasal; D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000517:prevention & control*; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000302:isolation & purification; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004802:Eosinophilia / Q000276:immunology / Q000517:prevention & control; D006358:Hot Temperature; D007114:Immunization; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D014373:Tuberculin / Q000008:administration & dosage
D000485:Allergens; D001500:BCG Vaccine; D014373:Tuberculin; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin