Long-Term Protective and Antigen-Specific Effect of Heat-Killed Mycobacterium vaccae in a Murine Model of Allergic Pulmonary Inflammation

Abstract

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-γ) 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-γ-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-γ, induces long term and Ag-specific protection, and therefore has both prophylactic and therapeutic potential for the treatment of allergic diseases.

Mycobacterium vaccae induces a population of pulmonary CD11c+ cells with regulatory potential in allergic mice

“…We report no changes in the expression levels of IL-12 and IFN-+ mRNA regardless of treatment. This confirms previous work by Zuany-Amorim and colleagues who showed in a similar model that the beneficial effects of M. vaccae are independent of IFN-+ [16]. Hence, rather than affecting the Th1/Th2 balance, M. vaccae regulates the allergic host immune responses through the induction of Tregs [17].…”

“…We were not surprised by the failure of M. vaccae to reduce total IgE levels in allergic mice soon after treatment. Other groups have made similar observations [16,24]. The lack of effect on IgE may be explained by a recent study showing the prolonged survival of memory plasma cells in specific areas of the bone marrow and spleen [25].…”

“…In experimental models of pulmonary inflammation, a saprophytic mycobacterium, Mycobacterium vaccae, has shown particular therapeutic potential. Treatment with M. vaccae significantly reduces murine allergic pulmonary inflammation by inducing CD4 + CD45RB low Tregs that secrete IL-10 and TGF-g [16,17]. These cells are allergen-specific, and upon passive transfer can protect recipient allergic mice from airway inflammation by significantly reducing eosinophilia in the lungs [17].…”

Role of dendritic cells: a step forward for the hygiene hypothesis

“…[58][59][60][61][62][63] The involvement of Tregs in bacterial infectionmediated modulation of allergy/asthma has been reported, but is much less studied. [64][65][66] In particular, subcutaneous treatment with heat-killed Mycobacterium vaccae was reported to induce CD4 1 CD45RB low T cells, which inhibited asthma through IL-10 and TGF-b production. 65,66 Therefore, microbial infections may modulate Th2-like allergic responses by promoting immune deviation (toward a Th1 response) and/ or enhancing immune regulation depending on the nature of the infectious agents, the extent/stages of the infections and the genetic background of the hosts.…”

<i>Mycobacterium vaccae</i> Immunization to Pregnant BALB/c Mice Ameliorated Lung Histopathology and Bone Marrow Eosinophila in Ovalbumin Sensitized Offsprings

“…M. vaccae is mainly being studied for use as an immunotherapeutic agent together with chemotherapy in the treatment of tuberculosis and other diseases, such as cancer, atopic dermatitis, and psoriasis [12]. Studies also showed that M. vaccae has been able to supress allergic and asthma-like responses in mice [13]- [15]. Furthermore, we demonstrated that treatment of newborn mice with heat-killed M. vaccae significantly reduced the number of goblet cells, the thickness of the basement membrane and subepithelial smooth muscle after subsequent allergen sensitization and challenge [16].…”