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IL-10 is a potent immunomodulatory cytokine that affects innate and acquired immune responses. The immunological consequences of IL-10 production during pulmonary tuberculosis (TB) are currently unknown, although IL-10 has been implicated in reactivation TB in humans and with TB disease in mice. Using Mycobacterium tuberculosis-susceptible CBA/J mice, we(More)
Failure of mice to produce IL-10 has no effect on the bacterial burden of Mycobacterium tuberculosis infection in the lungs over the first 4-5 months of the disease. We show here that after 185 days of the infection, IL-10 gene disrupted (IL-10 KO) mice showed evidence of bacterial regrowth, began to show signs of wasting, and were moribund. We assessed the(More)
In this study we demonstrate that it is possible to shift the immune system during a chronic infection with Mycobacterium tuberculosis. TGFβ and IL10 cytokines inhibit the Th1 response during chronic pulmonary infection with M. tuberculosis. We show that intrapulmonary delivery of siRNA targeting TGFβ1 is able to reduce the pulmonary bacillary load in mice(More)
Tuberculosis (TB), caused by the infection of Mycobacterium tuberculosis (Mtb), continues to pose a serious threat to public health, and the situation is worsening with the rapid emergence of multidrug resistant (MDR) TB. Current TB regimens require long duration of treatment, and their toxic side effects often lead to poor adherence and low success rates.(More)
Expression of viral and major histocompatibility complex (MHC) antigens and localization of T cells and macrophages was studied in frozen tissue sections of spleens taken from normal pigs or from pigs inoculated with highly virulent Lisbon 60 (L60), or with moderately virulent Dominican Republic 1978 (DR-II), African swine fever virus (ASFV) isolates.(More)
The production of immunosuppressive cytokines, such as IL-10 and TGF-beta, has been documented in individuals diagnosed with active tuberculosis. In addition, IL-10 production is increased within the lungs of mice that have chronic mycobacterial infection. Therefore, we hypothesized that the down-regulatory properties of IL-10 might contribute to the(More)
Highly vacuolated or foamy macrophages are a distinct characteristic of granulomas in the lungs of animals infected with Mycobacterium tuberculosis. To date these have usually been considered to represent activated macrophages derived from monocytes entering the lesions from the blood. However, we demonstrate in this study that foamy macrophages express(More)
In this study, we investigated the ability of four clinical isolates of Mycobacterium tuberculosis representing a range of virulence for their capacity to grow in bone marrow-derived macrophages. The rate of growth of each of the isolates in macrophages reflected their known virulence, but the most virulent isolates strongly induced production of the(More)
Analysis of T-cell subsets accumulating in the lungs of C57BL/6 mice chronically infected with Mycobacterium tuberculosis revealed that both CD4 and CD8 T-cell populations expressed a cell surface phenotype consistent with that of effector T cells and that a significant proportion of these cells were in the process of secreting gamma interferon.
A unique hallmark of tuberculosis is the granulomatous lesions formed in the lung. Granulomas can be heterogeneous in nature and can develop a necrotic, hypoxic core which is surrounded by an acellular, fibrotic rim. Studying bacilli in this in vivo microenvironment is problematic as Mycobacterium tuberculosis can change its phenotype and also become(More)