Recombinant Mycobacterium bovis BCG producing IL‐18 reduces IL‐5 production and bronchoalveolar eosinophilia induced by an allergic reaction

• Published in: Allergy (Copenhagen) Vol. 60; no. 8; pp. 1065 - 1072
• Main Authors: Biet, F., Duez, C., Kremer, L., Marquillies, P., Amniai, L., Tonnel, A.‐B., Locht, C., Pestel, J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Munksgaard International Publishers 01-08-2005; Blackwell; Wiley
• Subjects: Allergic diseases; allergy; Animals; Bacillus Calmette‐Guérin; BCG Vaccine - metabolism; Biological and medical sciences; Bronchi - pathology; cytokines; Eosinophilia - etiology; Eosinophilia - prevention & control; eosinophils; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hypersensitivity - complications; Immunopathology; Interleukin-18 - biosynthesis; Interleukin-5 - antagonists & inhibitors; Interleukin-5 - biosynthesis; Life Sciences; Lymph Nodes - metabolism; Medical sciences; Mice; Mice, Inbred BALB C; Mycobacterium bovis; Pulmonary Alveoli - pathology; Th1/Th2; Vaccines, Synthetic - metabolism; Th1/Th2; Immunopathology; Allergy; Mycobacterium bovis; BCG; Cytokine; Granulocyte; Th1 lymphocyte; eosinophils; Hemopathy; Eosinophilia; Eosinophil; Interleukin 18; Bacillus Calmette-Guerin; Immunology; Interleukin 5; Mycobacteriales; Mycobacteriaceae; Bacteria; Actinomycetes; Th2 lymphocyte; cytokines; Recombinant protein
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/j.1398-9995.2005.00826.x

Background:  Allergic reactions occur through the exacerbated induction of a Th2 cell type expression profile and can be prevented by agents favoring a Th1 profile. Bacillus Calmette‐Guérin (BCG) is able to induce high IFN‐γ levels and has been shown to decrease experimentally induced allergy. The induction of IFN‐γ is mediated by interleukin (IL)‐12 known to be secreted upon mycobacterial infections and can be enhanced by IL‐18 acting in synergy with IL‐12.
Objective:  We evaluated the ability of a recombinant BCG strain producing IL‐18 (rBCG) to modify the Th2 type responses in a murine model of ovalbumin (OVA)‐dependent allergic reaction.
Methods:  Mice were injected intraperitoneally or intranasally with OVA at days 0 and 15 and exposed to an OVA aerosol challenge at days 29, 30, 31 and 34. At days 0 and 15, two additional groups of mice received OVA together with 5 × 106 colony forming units of either rBCG or nonrecombinant BCG.
Results:  A time‐course analysis of OVA‐specific immunoglobulin (Ig)E, IgG1 and IgG2a levels indicated no significant difference between the three groups of mice. However, following in vitro stimulation with OVA, lymph node cells from rBCG‐treated mice produced less IL‐5 and more IFN‐γ than those of mice injected with nonrecombinant BCG. In addition, 48 h after the last OVA challenge, a strong reduction of bronchoalveolar eosinophilia was found in the rBCG‐injected mice compared to the nontreated or nonrecombinant BCG‐treated groups.
Conclusion:  These results indicate that the production of IL‐18 by rBCG may enhance the immunomodulatory properties of BCG that suppress pulmonary Th2 responses and, in particular, decrease airway eosinophilia.