Intracellular growth of Mycobacterium avium in human macrophages is linked to the increased synthesis of prostaglandin E2 and inhibition of the phagosome-lysosome fusions.
A virulent strain of Mycobacterium avium grew actively inside human adherent peripheral blood monocyte-derived macrophages. Bacteria were always confined to the phagosome compartment and were encapsulated. Cytochemical labeling of acid phosphatase using transmission electron microscopy showed a strong inhibition of the phagosome-lysosome fusions (PLF) in macrophages as not more than 25-30% bacteria containing phagosome at any time effectively fused with lysosomes. In case of a positive fusion event, the bacterial capsule prevented the diffusion of the lysosomal contents to the bacterial surface. Moreover, the infection of macrophages both by living and gamma-killed M. avium was linked to an increased synthesis of prostaglandin E2 (PGE2); however the total amount of PGE2 synthesized in the latter case was significantly lower than that observed with viable organisms. Our results suggest that the inability of human macrophages to control M. avium infection is linked to immunosuppressive pathways, e.g. enhanced synthesis of PGE2 and also to an impairment of normal microbicidal functions of the infected macrophages.
Rastogi
N
N
Unité de la Tuberculose et des Mycobactéries, Institut Pasteur, Paris, France.
Bachelet
M
M
Carvalho de Sousa
J P
JP
D000135:Acid Phosphatase / Q000032:analysis; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis*; D005720:Gamma Rays; D006801:Humans; D007108:Immune Tolerance; D008247:Lysosomes / Q000382:microbiology*; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology* / Q000648:ultrastructure; D008561:Membrane Fusion; D008854:Microscopy, Electron; D009162:Mycobacterium avium / Q000254:growth & development* / Q000528:radiation effects; D010587:Phagocytosis
D000135:Acid Phosphatase; D015232:Dinoprostone