Long-term protective and antigen-specific effect of heat-killed Mycobacterium vaccae in a murine model of allergic pulmonary inflammation.
This report examines the effect of heat-killed Mycobacterium vaccae in a mouse model of allergic pulmonary inflammation. The s.c. administration of M. vaccae 3 wk before the immunization significantly reduced Ag-induced airway hyperreactivity and the increase in the numbers of eosinophils observed in the bronchoalveolar lavage fluid, blood, and bone marrow, even though no detectable changes in either cytokine (IL-4, IL-13, IL-5, and IFN-gamma) or total IgE levels were observed. Furthermore, transfer of splenocytes from OVA-immunized and M. vaccae-treated mice into recipient, OVA-immunized mice significantly reduced the allergen-induced eosinophilia by an IFN-gamma-independent mechanism, clearly indicating that the mechanism by which M. vaccae induces its inhibitory effect is not due to a redirection from a predominantly Th2 to a Th1-dominated immune response. The protective effect of M. vaccae on the allergen-induced eosinophilia lasted for at least 12 wk after its administration, and the treatment was also effective in presensitized mice. Moreover, the allergen specificity of the inhibitory effect could be demonstrated using a double-immunization protocol, where M. vaccae treatment before OVA immunization had no effect on the eosinophilic inflammation induced by later immunization and challenge with cockroach extract Ag. Taken together, these results clearly demonstrate that M. vaccae is effective in blocking allergic inflammation by a mechanism independent of IFN-gamma, induces long term and Ag-specific protection, and therefore has both prophylactic and therapeutic potential for the treatment of allergic diseases.
Novartis Horsham Research Center, Novartis Pharmaceutical Ltd., Horsham, United Kingdom. claudia.zuany_amorim_fromond@pharma.novartis.com
Claudia
C
Zuany-Amorim
Corinne
C
Manlius
Alexandre
A
Trifilieff
Laura R
LR
Brunet
Graham
G
Rook
Gareth
G
Bowen
Graham
G
Pay
Christoph
C
Walker
D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000517:prevention & control*; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004802:Eosinophilia / Q000517:prevention & control; D004804:Eosinophils / Q000502:physiology; D005260:Female; D006967:Hypersensitivity / Q000517:prevention & control*; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D007249:Inflammation / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D015164:Vaccines, Inactivated / Q000276:immunology
D000941:Antigens; D001428:Bacterial Vaccines; C408982:CPG-oligonucleotide; D018925:Chemokines; D016207:Cytokines; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D015164:Vaccines, Inactivated; D007073:Immunoglobulin E; D010047:Ovalbumin