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Epidemiological and experimental evidence supports the notion that microbial infections that are known to induce Th1-type immune responses can suppress Th2 immune responses, which are characteristics of allergic disorders. However, live microbial immunization might not be feasible for human immunotherapy. Here, we evaluated whether induction of Th1 immunity by the immunostimulatory sequences of CpG-oligodeoxynucleotides (CpG-ODN), with or without culture filtrate proteins (CFP), from Mycobacterium tuberculosis would suppress ongoing allergic lung disease. Presensitized and ovalbumin (OVA)-challenged mice were treated subcutaneously with CpG, or CpG in combination with CFP (CpG/CFP). After 15 days of treatment, airway inflammation and specific T- and B-cell responses were determined. Cell transfer experiments were also performed. CpG treatment attenuated airway allergic disease; however, the combination CpG/CFP treatment was significantly more effective in decreasing airway hyperresponsiveness, eosinophilia and Th2 response. When an additional intranasal dose of CFP was given, allergy was even more attenuated. The CpG/CFP therapy also reduced allergen-specific IgG1 and IgE antibodies and increased IgG2a. Transfer of spleen cells from mice immunized with CpG/CFP also reduced allergic lung inflammation. CpG/CFP treatment induced CFP-specific production of IFN-γ and IL-10 by spleen cells and increased production of IFN-γ in response to OVA. The essential role of IFN-γ for the therapeutic effect of CpG/CFP was evidenced in IFN-γ knockout mice. These results show that CpG/CFP treatment reverses established Th2 allergic responses by an IFN-γ-dependent mechanism that seems to act both locally in the lung and systemically to decrease allergen-specific Th2 responses.

Mycobacterium tuberculosis and helminth infections coincide geographically and are classically described as TH1 and TH2 pathologies. There is much interest in exploring how concurrent worm infections might alter immune responses to mycobacterial infection. To explore this issue, mice were infected with Toxocara canis and co-infected with M. tuberculosis. Mice infected with M. tuberculosis had high numbers of neutrophils and mononuclear cells within the alveolar spaces, with increased parenchymal interferon (IFN)-gamma levels. However, in Toxocara-infected mice we detected increased eosinophil numbers in bronchoalveolar lavage fluid (BALF) and increased parenchymal levels of interleukin (IL)-5. In co-infected mice the BALF demonstrated enhanced eosinophil influx with decreased neutrophil and mononuclear cell accumulation. However, co-infected mice had similar mycobacterial proliferation in their lungs accompanied by similar histopathological changes and similar cytokine/nitric oxide production compared with Mycobacterium-only-infected mice. Our results suggest that T. canis infection does not necessarily lead to increased susceptibility to pulmonary tuberculosis.