IL-10 and NOS2 modulate antigen-specific reactivity and nerve infiltration by T cells in experimental leprosy.

Abstract

BackgroundAlthough immunopathology dictates clinical outcome in leprosy, the dynamics of early and chronic infection are poorly defined. In the tuberculoid region of the spectrum, Mycobacterium leprae growth is restricted yet a severe granulomatous lesion can occur. The evolution and maintenance of chronic inflammatory processes like those observed in the leprosy granuloma involve an ongoing network of communications via cytokines. IL-10 has immunosuppressive properties and IL-10 genetic variants have been associated with leprosy development and reactions.Methodology/principal findingsThe role of IL-10 in resistance and inflammation in leprosy was investigated using Mycobacterium leprae infection of mice deficient in IL-10 (IL-10-/-), as well as mice deficient in both inducible nitric oxide synthase (NOS2-/-) and IL-10 (10NOS2-/-). Although a lack of IL-10 did not affect M. leprae multiplication in the footpads (FP), inflammation increased from C57Bl/6 (B6)Conclusions/significanceThe 10NOS2-/- strain offers insight on the regulation of granuloma formation and maintenance by immune modulators in the resistant forms of leprosy and presents a new model for investigating the pathogenesis of neurological involvement.