Effect of pre‐immunization by killed Mycobacterium bovis and vaccae on immunoglobulin E response in ovalbumin‐sensitized newborn mice

Abstract

A recently advanced hypothesis suggests that decreased exposure to T-helper (Th) 1-inducing agents causes Th2-biased differentiation in response to concomitant allergens. We therefore examined the effect of pre-immunization with killed Mycobacterium bovis and killed M. vaccae which are known to be very potent inducers of Thl immune response, on serum IgE response in ovalbumin (OVA)-sensitized newborn mice. Eighty-four newborn Balb/c mice were divided into four groups and were immunized intraperitoneally 24 h after birth with 50 microl of 5 x 10(4) colony-forming units (c.f.u.) of killed M. bovis in group I (M. bovis group, n = 19), with 25 microl of 2.5 x 10(8) c.f.u. of killed M. vaccae plus 25 microl of 5 x 10(4) c.f.u. of killed M. bovis in group II (M. vaccae + M. bovis group, n = 28) and with 50 microl of only phosphate-buffered saline (PBS) in group III (no mycobacterial immunization, n = 18). No injection was applied to mice in group IV (control group, n = 19). Starting from 8 weeks of age, all mice except the control group were sensitized with 0.5 ml of 20 mg/ml OVA administered intraperitoneally 7 times every other day. Thirty days after the final injection, all animals except those in the control group were challenged with an aerosol of 2 mg/ml OVA. Forty-eight hours later, blood was collected from all mice for determination of serum IgE levels. A statistically significant difference was observed in the serum total IgE levels between groups III and IV (p = 0.0099), indicating that the mice were successfully sensitized with OVA. Serum total IgE values of the female mice in M. bovis group were found to be significantly lower than group III (p = 0.009), while no difference was observed in males. Serum total IgE levels of the M. vaccae + M. bovis group were found to be significantly lower than group III both in male and female mice (p < 0.0001 and p = 0.0001, respectively). Female values were even lower than controls (p = 0.0092). Pre-immunization in the newborn period with killed M. bovis alone or in addition to M. vaccae may potentially be helpful in down-regulating an IgE response.

Airway Hyperresponsiveness, Late Allergic Response, and Eosinophilia Are Reversed with Mycobacterial Antigens in Ovalbumin-Presensitized Mice

“…In addition to us, others have demonstrated a suppressive effect on various parameters of allergic inflammation in mouse models after mycobacteria pretreatment (4,5,8,9). However, except for one report from the work of Wang and Rook (7), there is no information as to the potential for these Ags in attenuating a preexisting allergic state.…”

Imprinted DC mediate the immune‐educating effect of early‐life microbial exposure

“…Although numerous reported epidemiological and experimental studies have demonstrated the inhibitory role of live or killed microbes or microbial components on allergic responses [18][19][20][21][22][23][24][25], the basis for this inhibition remains unclear. In particular, little experimental study has been performed on the effect and mechanism of neonatal microbial exposure on airway allergic inflammation.…”

Epidemiological and immunological evidence for the hygiene hypothesis

“…However, preceding or concomitant activation of cells of the innate immune system with whole bacteria or bacterial-derived TLR ligands has been shown to effectively prevent allergic sensitization and/or allergic inflammation following local allergen challenge. For example, Tu¨kenmez et al observed that total IgE titers after an ovalbumin (OVA) sensitization were reduced in animals that have been preimmunized to heat-killed Mycobacterium bovis immediately after birth (Tukenmez et al, 1999). This is accompanied by attenuated histopathological changes following intratracheal allergen challenge (Ozdemir et al, 2003).…”