Increased interleukin-10 expression is not responsible for failure of T helper 1 immunity to resolve airborne Mycobacterium tuberculosis infection in mice

Abstract

With a view to determining whether failure of mice to resolve Mycobacterium tuberculosis (Mtb) infection is a consequence of downregulation of T helper 1 (Th1) immunity by interleukin (IL)-10, mice deleted of the gene for IL-10 were compared with wild-type (WT) mice in terms of their ability to make IL-10 mRNA, generate Th1-mediated immunity [as measured by synthesis of mRNA for interferon-gamma (IFN-gamma)], IL-12p40 and inducible nitric oxide synthase (iNOS), and to control lung infection. It was found that the response of WT mice to infection included a substantial and sustained increase in IL-10 mRNA synthesis in the lungs. A Th1 response in the lungs of WT and IL-10-/- mice was evidenced by a large and sustained increase in the synthesis of mRNA for IFN-gamma, IL-12p40 and iNOS, with somewhat higher levels of these mRNA species being made in the lungs of IL-10-/- mice, particularly at an early stage of infection. However, IL-10-/- mice were no more capable than WT mice at combating infection.

Figure 1

Growth of Mycobacterium tuberculosis (Mtb) in the lungs of wild-type (WT) versus interleukin (IL)-10^−/− mice infected with 10² colony-forming units (CFU) of Mtb via the respiratory route. IL-10^−/− mice were found to be identical to WT mice in their ability to control lung infection. In both types of mice, Mtb grew progressively for 20 days, after which infection was maintained at a stationary level until the experiment was stopped on day 100. The mean values ± standard deviation (SD) of five mice per group are shown.

Figure 2

Change in interleukin (IL)-10, IL-12p40, interferon-γ (IFN-γ) and inducible nitric oxide synthase (iNOS) gene expression in the lungs of Mycobacterium tuberculosis (Mtb)-infected IL-10^−/− and wild-type (WT) mice against time of infection. Inhibition of further Mtb growth in WT mice (as shown in Fig. 1) was associated with a substantial increase in IL-10 mRNA synthesis in the lungs, which was sustained until the experiment was stopped on day 100. Inhibition of Mtb growth was also associated with the expression of T helper (Th1) immunity, as evidenced by a substantial increase in the synthesis of mRNA for IL-12p40, IFN-γ and iNOS, which was sustained until the experiment was stopped. A higher level of synthesis of these mRNA species occurred in the lungs of IL-10^−/− mice at day 20 of infection and probably at day 50. The mean values ± standard deviation (SD) of four mice per group, at each time-point, are shown.