Recombinant Mycobacterium bovis BCG producing IL-18 reduces IL-5 production and bronchoalveolar eosinophilia induced by an allergic reaction.
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-gamma levels and has been shown to decrease experimentally induced allergy. The induction of IFN-gamma 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 x 10(6) 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-gamma 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.


CONCLUSIONS
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.
Biet
F
F
Laboratoire de Microbiologie Génétique et Moléculaire, INSERM U629, Lille, France.
Duez
C
C
Kremer
L
L
Marquillies
P
P
Amniai
L
L
Tonnel
A-B
AB
Locht
C
C
Pestel
J
J
D000818:Animals; D001500:BCG Vaccine / Q000378:metabolism*; D001980:Bronchi / Q000473:pathology*; D004802:Eosinophilia / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D006967:Hypersensitivity / Q000150:complications*; D020382:Interleukin-18 / Q000096:biosynthesis*; D015848:Interleukin-5 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011650:Pulmonary Alveoli / Q000473:pathology*; D014614:Vaccines, Synthetic / Q000378:metabolism
D001500:BCG Vaccine; D020382:Interleukin-18; D015848:Interleukin-5; D014614:Vaccines, Synthetic