Intracellular Mycobacterium avium Intersect Transferrin in the Rab11+ Recycling Endocytic Pathway and Avoid Lipocalin 2 Trafficking to the Lysosomal Pathway

Iron is an essential nutrient for microbes, and many pathogenic bacteria depend on siderophores to obtain iron. The mammalian innate immunity protein lipocalin 2 (Lcn2; also known as neutrophil gelatinase-associated lipocalin, 24p3, or siderocalin) binds the siderophore carboxymycobactin, an essenti...

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Published in:The Journal of infectious diseases 2010-03, Vol.201 (5), p.783-792
Main Authors: Halaas, Øyvind, Steigedal, Magnus, Haug, Markus, Awuh, Jane A., Ryan, Liv, Brech, Andreas, Sato, Shintaro, Husebye, Harald, Cangelosi, Gerard A., Akira, Shizuo, Strong, Roland K., Espevik, Terje, Flo, Trude H.
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Language:English
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Summary:Iron is an essential nutrient for microbes, and many pathogenic bacteria depend on siderophores to obtain iron. The mammalian innate immunity protein lipocalin 2 (Lcn2; also known as neutrophil gelatinase-associated lipocalin, 24p3, or siderocalin) binds the siderophore carboxymycobactin, an essential component of the iron acquisition apparatus of mycobacteria. Here we show that Lcn2 suppressed growth of Mycobacterium avium in culture, and M. avium induced Lcn2 production from mouse macrophages. Lcn2 also had elevated levels and initially limited the growth of M. avium in the blood of infected mice but did not impede growth in tissues and during long-term infections. M. avium is an intracellular pathogen. Subcellular imaging of infected macrophages revealed that Lcn2 trafficked to lysosomes separate from M. avium, whereas transferrin was efficiently transported to the mycobacteria. Thus, mycobacteria seem to reside in the Rab11+ endocytic recycling pathway, thereby retaining access to nutrition and avoiding endocytosed immunoproteins like Lcn2.
ISSN:0022-1899
1573-6613
1537-6613
DOI:10.1086/650493