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

• 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.
• Format: Article
• Language: English
• Subjects: Acute-Phase Proteins - immunology; Acute-Phase Proteins - metabolism; Animals; Bacteria; Bacteriology; Biological and medical sciences; Blood - microbiology; Colony Count, Microbial; Endosomes; Fundamental and applied biological sciences. Psychology; Infections; Infectious diseases; Iron; Lipocalin-2; Lipocalins - blood; Lipocalins - immunology; Lipocalins - metabolism; Liver - microbiology; Lysosomes; Lysosomes - chemistry; Lysosomes - metabolism; Lysosomes - microbiology; Macrophages; Macrophages - immunology; Macrophages - microbiology; Medical sciences; Mice; Mice, Inbred C57BL; Microbiology; Miscellaneous; Mycobacterium avium - growth & development; Mycobacterium avium - immunology; Mycobacterium avium - metabolism; Mycobacterium avium - pathogenicity; Mycobacterium tuberculosis; Neutrophils; Oncogene Proteins - blood; Oncogene Proteins - immunology; Oncogene Proteins - metabolism; Phagosomes; rab GTP-Binding Proteins - metabolism; Spleen - microbiology; Transferrin - metabolism; Transferrins; Tuberculosis - immunology; Tuberculosis - microbiology
• ISSN: 0022-1899; 1573-6613; 1537-6613
• DOI: 10.1086/650493

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.