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The control of Mycobacterium tuberculosis infection depends on recognition of the pathogen and the activation of both the innate and adaptive immune responses. Toll-like receptors (TLR) were shown to play a critical role in the recognition of several pathogens. Mycobacterial antigens recognise distinct TLR resulting in rapid activation of cells of the(More)
TNF-deficient mice are highly susceptible to Mycobacterium tuberculosis H37Rv infection. Here we asked whether TNF is required for postinfectious immunity in aerosol-infected mice. Chemotherapy for 4 wk commencing 2 wk postinfection reduced CFU to undetectable levels. While wild-type mice had a slight rise in CFU, but controlled infection upon cessation of(More)
The dynamics of host-pathogen interactions have important implications for the design of new antimicrobial agents to treat chronic infections such as tuberculosis (TB), which is notoriously refractory to conventional drug therapy. In the mouse model of TB, an acute phase of exponential bacterial growth in the lungs is followed by a chronic phase(More)
Exposure to Mycobacterium tuberculosis results in clinical tuberculosis only in a small percentage of healthy individuals. In most instances the bacilli are controlled by the immune system and survive in a latent state within granuloma. Immunosuppression, however, may result in reactivation of infection, resulting in clinical disease. Using a low-dose(More)
Tumor necrosis factor (TNF) is critical and non-redundant to control Mycobacterium tuberculosis infection and cannot be replaced by other proinflammatory cytokines. Overproduction of TNF may cause immunopathology, while TNF neutralization reactivates latent and chronic, controlled infection, which is relevant for the use of neutralizing TNF therapies in(More)
Toll-like receptors (TLRs) play a critical role in the recognition of several pathogens, including Mycobacterium tuberculosis. Mycobacterial antigens recognize distinct TLRs resulting in rapid activation of cells of the innate immune system. Ablation of most of the TLR signalling as in mice deficient for the common adaptor protein MyD88 reveals that TLR is(More)
Tumor necrosis factor (TNF) is required in the control of infection with Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. TNF is essential and non-redundant for forming microbiocidal granulomas, and cannot be replaced by other members of the TNF family. We established a model of latent Mtb infection in mice, allowing investigation of(More)
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(More)
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(More)
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