Infection of Mice with Mycobacterium bovis–Bacillus Calmette-Guérin (BCG) Suppresses Allergen-induced Airway Eosinophilia

Abstract

It has been proposed that the increase in prevalence and severity of atopic disorders inversely correlates with exposure to infectious diseases such as tuberculosis. We have investigated this issue by combining an intranasal Mycobacterium bovis–Bacillus Calmette-Guérin (BCG) infection with a murine model of allergen, (ovalbumin [OVA]) induced airway eosinophilia. BCG infection either 4 or 12 wk before allergen airway challenge resulted in a 90–95 and 60–70% reduction in eosinophilia within the lungs, respectively, compared to uninfected controls. The inhibition of airway eosinophilia correlated with a reduced level of IL-5 production by T cells from the lymph node draining the site of OVA challenge. Interestingly, BCG infection of the lung had no effect on IgG1 and IgE OVA-specific serum immunoglobulin or blood eosinophil levels. Furthermore, BCG-induced inhibition of airway eosinophilia was strongly reduced in interferon (IFN)-γ receptor–deficient mice and could be partially reversed by intranasal IL-5 application. Intranasal BCG infections could also reduce the degree of lung eosinophilia and IL-5 produced by T cells after Nippostrongylus brasiliensis infection. Taken together, our data suggest that IFN-γ produced during the T helper cell (Th)1 immune response against BCG suppresses the development of local inflammatory Th2 responses in the lung. Most importantly, this inhibition did not extend to the systemic immunoglobulin response against OVA. Our data support the view that mycobacterial infections have the potential to suppress the development of atopic disorders in humans.

Asthma and atopy – the price of affluence?

“…The immunological basis and the mechanisms that are thought to operate in this immunomodulation, have been discussed in detail in several recent reviews and will not be reiterated here (49)(50)(51)(52)(53)(54). In addition, a number of animal experiments have provided support for the hygiene hypothesis (55)(56)(57)(58), but these data are also beyond the scope of this review.…”

Ramp-ing up allergies: Nramp1 (Slc11a1), macrophages and the hygiene hypothesis

“…The candidature of mycobacteria was derived from experiments in animal models, in which bacillus Calmette-Guérin (BCG) or heat-killed Mycobacterium vaccae significantly reduced allergic and asthmatic manifestations [11,12]. By contrast, studies investigating the possible correlation between mycobacterial vaccination during early infancy or maturity and the subsequent development of atopy or asthma in humans are conflicting (reviewed in Ref.…”

A single administration of interleukin-4 antagonistic mutant DNA inhibits allergic airway inflammation in a mouse model of asthma

“…The administration of various bacteria that can induce Th1-type immune responses has also been reported to inhibit the development of allergic-induced AHR. 40,41 These mechanisms have indirect inhibitory effects on the development of allergic AHR, since sensitization of hosts to a few species of bacteria, such as mycobacteria species, which can induce immune responses results in the elicitation of bacteria-specific Th1-type immune responses.…”