Gemfibrozil inhibits Legionella pneumophila and Mycobacterium tuberculosis enoyl coenzyme A reductases and blocks intracellular growth of these bacteria in macrophages.

We report here that gemfibrozil (GFZ) inhibits axenic and intracellular growth of Legionella pneumophila and of 27 strains of wild-type and multidrug-resistant Mycobacterium tuberculosis in bacteriological medium and in human and mouse macrophages, respectively. At a concentration of 0.4 mM, GFZ completely inhibited L.

Mycobacterium tuberculosis H37Ra and H37Rv differential growth and cytokine/chemokine induction in murine macrophages in vitro.

The role of tumor necrosis factor-alpha (TNF-alpha) in controlling growth of Mycobacterium tuberculosis in murine peritoneal macrophages infected in vitro was studied. TNF-alpha was shown to be required but not sufficient, and the amount of TNF-alpha produced by the infected cells did not correlate with the extent of growth control. In this system, TNF-alpha-dependent control of growth of the avirulent strain H37Ra was independent of inducible nitric oxide synthase (iNOS) and interferon-gamma (IFN-gamma), as shown by the infection of macrophages from selected gene-disrupted mice.

Hypervirulent M. tuberculosis W/Beijing strains upregulate type I IFNs and increase expression of negative regulators of the Jak-Stat pathway.

The role of type I interferons (IFNs) in the host response to bacterial infections is controversial. Here, we examined the role of IFN-alpha/beta in the murine response to infection with Mycobacterium tuberculosis, using wildtype mice, mice with impaired signaling through the type I IFN receptor (IFNAR), and mice treated to reduce levels of type I IFNs. In this study, we used virulent clinical isolates of M.

Differential monocyte activation underlies strain-specific Mycobacterium tuberculosis pathogenesis.

In vitro infection of monocytes with Mycobacterium tuberculosis HN878 and related W/Beijing isolates preferentially induced interleukin-4 (IL-4) and IL-13, which characterize Th2 polarized immunity. In contrast, CDC1551 induced more IL-12 and other molecules associated with phagocyte activation and Th1 protective immunity. The differential cytokine-chemokine response was mediated by extracted lipids, suggesting that these molecules regulate host responses to infection.

Interleukin-10 (IL-10) in experimental visceral leishmaniasis and IL-10 receptor blockade as immunotherapy.

Interleukin-10 (IL-10) is thought to promote intracellular infection, including human visceral leishmaniasis, by disabling Th1 cell-type responses and/or deactivating parasitized tissue macrophages. To develop a rationale for IL-10 inhibition as treatment in visceral infection, Th1 cytokine-driven responses were characterized in Leishmania donovani-infected BALB/c mice in which IL-10 was absent or overexpressed or its receptor (IL-10R) was blockaded. IL-10 knockout and normal mice treated prophylactically with anti-IL-10R demonstrated accelerated granuloma assembly and rapid parasite killing without untoward tissue inflammation; IL-12 and gamma interferon mRNA expression, inducible nitric oxide synthase reactivity, and responsiveness to antimony chemotherapy were also enhanced in knockout mice.

Mycobacterial antigens exacerbate disease manifestations in Mycobacterium tuberculosis-infected mice.

To control tuberculosis worldwide, the burden of adult pulmonary disease must be reduced. Although widely used, Mycobacterium bovis BCG vaccination given at birth does not protect against adult pulmonary disease. Therefore, postexposure vaccination of adults with mycobacterial antigens is being considered.