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 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.
Halaas
Oyvind
O
Department of Cancer Research and Molecular Medicine, Norges Teknisk-Naturvitenskapelige Universitet, and St. Olavs Hospital, Trondheim, Norway.
Steigedal
Magnus
M
Haug
Markus
M
Awuh
Jane A
JA
Ryan
Liv
L
Brech
Andreas
A
Sato
Shintaro
S
Husebye
Harald
H
Cangelosi
Gerard A
GA
Akira
Shizuo
S
Strong
Roland K
RK
Espevik
Terje
T
Flo
Trude H
TH
D000209:Acute-Phase Proteins / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D001769:Blood / Q000382:microbiology; D015169:Colony Count, Microbial; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D008099:Liver / Q000382:microbiology; D008247:Lysosomes / Q000737:chemistry / Q000378:metabolism* / Q000382:microbiology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009162:Mycobacterium avium / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity*; D015513:Oncogene Proteins / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D013154:Spleen / Q000382:microbiology; D014168:Transferrin / Q000378:metabolism*; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
D000209:Acute-Phase Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D014168:Transferrin; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C071332:Lcn2 protein, mouse