Beta-2-microglobulin-deficient mice: increased susceptibility to Mycobacterium avium infection
Abstract number: 1733_1236
Gomes Pereira S., Rodrigues P., Appelberg R., Gomes S.
Iron availability is critical for mycobacterial survival and multiplication, with host iron overload favouring bacterial growth and increasing susceptibility. Previous studies have shown that beta-2-microglobulin-deficient mice (b2m KO) are highly susceptible to M. tuberculosis infection, which was in part due to the absence of CD8+ T cells but also to the iron overload typical of b2m KO hepatocytes. In M. avium infection, CD8+ T cells are not fundamental for the control of bacterial growth, whereas an excess of iron is beneficial for its proliferation. Hfe-knock-out animals, on the other hand, represent a model of systemic iron overload, in the absence of any known immune deficiency.
In this study, we evaluated the susceptibility to M. avium infection of both b2mKO and HfeKO mice.
Age-matched animals from C57Bl/6 (wild-type), b2m KO and Hfe KO mouse strains were infected with M. avium strain 2447 SmT by the intravenous route. At different times post-infection, blood was collected for the quantification of serum iron and transferrin saturation. Spleen and liver were recovered for mycobacteria CFU counts, iron content determination and histological analysis (Ziehl-Nielssen, Perl's staining).
Two months after infection, b2m KO mice began to show higher hepatic mycobacteria counts when compared to wild-type animals. This difference was even more pronounced 4 months post-infection. In the liver, non-hemic iron values were about four-times higher in b2m KO animals than in wild-type controls, Serum iron and transferrin saturation were also higher in b2m-deficient mice. Spleen iron content did not show significant differences between these two strains. The increased susceptibility of b2mKO mice to M. avium infection does not result exclusively from the iron overload status of b2m KO mice. Hfe KO mice, which show similar iron levels and tissue distribution, also exhibited higher mycobacterial counts than wild-type animals, but did not show the same degree of susceptibility as b2m KO mice. In order to understand if CD8 T cells deficiency is contributing to the increased susceptibility in b2m KO animals, experiments with CD8 T cells depletion in Hfe KO mice are being carried out.
|Session name:||European Society of Clinical Microbiology and Infectious Diseases|
|Location:||ICC, Munich, Germany|
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