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

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2010 Feb 4

PMID 20121435

Citations 41

Authors

Oyvind Halaas

Magnus Steigedal

Markus Haug

Jane A Awuh

Liv Ryan

Andreas Brech

Shintaro Sato

Harald Husebye

Gerard A Cangelosi

Shizuo Akira

Roland K Strong

Terje Espevik

Trude H Flo

Affiliations

Soon will be listed here.

Abstract

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.

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