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Microbial products including mycobacterial antigens are recognized by distinct Toll-like receptors (TLRs) resulting in activation of cells of the innate immune system. Ablation of most of the TLR signalling in mice deficient for the common adaptor protein MyD88 revealed that TLRs are crucial for the activation of an innate immune response as MyD88-deficient mice are highly sensitive to infection with Mycobacterium tuberculosis. Despite the profound defect of the innate immune response, MyD88 deficiency allows the emergence of an adaptive immunity. These data demonstrate that activation of multiple TLRs contributes to an efficient innate response to mycobacteria, while MyD88-dependent signalling is dispensable to generate adaptive immunity.

We compared the growth levels and pathogenicities of the Mycobacterium tuberculosis MT103 clinical strain with those of the DeltapurC mutant strain MYC1551, which is auxotrophic for purine in wild-type and gamma interferon receptor (IFN-gammaR)-deficient mice. The DeltapurC strain MYC1551 grew initially in both wild-type and IFN-gammaR-deficient mice upon aerosol infection, but it grew much less than strain MT103 did. Despite the comparable bacterial burdens of the mice, IFN-gammaR-deficient mice succumbed to infection with DeltapurC strain MYC1551 from necrotic pneumonia within 6 weeks of those infected with MT103. In conclusion, the DeltapurC mutant MYC1551 displays reduced growth but retains pathogenicity. Therefore, the use of mutant strains of M. tuberculosis as live vaccines may not be recommended.