Interleukin-10 production by lung macrophages in CBA xid mutant mice infected with Mycobacterium tuberculosis Introduction It is well established that mice need to mount a T helper type 1 (Th1) response, mediated by the cytokines interleukin- 12 (IL-12), IL-23, and interferon-c (IFN-c), to successfully express host resistance to infection with Mycobacterium tuberculosis.1–5 In contrast, a Th2 response is not protective, although it remains unclear to what extent it might interfere with the overall course of the disease. Most evidence in the mouse model favours a lack of involvement in the expression of initial protective immunity,6,7 whereas much later during the disease process lung macrophages accumulate large amounts of IL-10 in mouse strains prone to reactivation disease.8 This includes mice on the CBA background of inbred strains. In this mouse, a well characterized mutation designated xid in the cytoplasmic signalling enzyme Bruton’s protein kinase
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Mice on the CBA inbred strain background expressing the well characterized mutation designated xid in the cytoplasmic signalling enzyme Bruton’s protein kinase have been previously noted to illustrate shifts in T helper type 1 (Th1)/Th2 immunity which is underlined by an apparent failure to produce the regulatory cytokine interleukin-10. In the current study we examined if this extended to infection with Mycobacterium tuberculosis, which also depends on Th1 immunity. Contrary to expectations, xid mice showed evidence of a transient early susceptibility to pulmonary infection, changes in macrophage morphology, and decreased activation of lung natural killer cells, while showing evidence of substantial IL-10 production and accumulation in lung lesions macrophages, but paradoxically this did not influence the course of the chronic disease. In addition, macrophages from the lungs of xid mice also expressed high levels of CD14. These observations suggest that the xid mutation in cellular signalling has much wider effects on the immune system than previously thought.
Interleukin-10, Xid mutation, Macrophages, Natural killer cells, T helper type 1 immunity, Tuberculosis
JUNQUEIRA-KIPNIS, Ana Paula et al. Interleukin-10 production by lung macrophages in CBA xid mutant mice infected with Mycobacterium tuberculosis. Immunology, Oxford, v. 115, n. 2, p. 246-252, 2005.