FEMS MicrobiologyImmunology89 (1992) 273-280 © 1992 Federation of European Microbiological Societies 0920-8534/92/$05.00 Published by Elsevier 273 FEMSIM 00216 Intracellular growth of Mycobacterium avium in human macrophages is linked to the increased synthesis of prostaglandin E 2 and inhibition of the phagosome-lysosome fusions Nalin Rastogi a Maria Bachelet b and J.P Carvalho de Sousa a a Unitd de la Tuberculose et des Mycobact&ies, and b Unitd de Pharmacologic Cdllulaire, lnstitut Pasteur, Paris, France Received 29 November 1991 Revision received 25 March 1992 Accepted 27 March 1992 Key words: Macrophage; Mycobacterium avium; Prostaglandin E2; Phagosome-lysosome fusion 1. SUMMARY A virulent strain of Mycobacterium avium grew actively inside human adherent peripheral blood monocyte-derived macrophages. Bacteria were al- ways confined to the phagosome compartment and were encapsulated. Cytochemical labeling of acid phosphatase using transmission electron mi- croscopy showed a strong inhibition of the phago- some-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. More- over, the infection of macrophages both by living and y-killed M. a~,ium was linked to an increased Correspondence to: N. Rastogi, Unitfi de la Tuberculose et des Mycobact~ries, Institut Pasteur, 25 Rue du Dr. Roux, 75724 Paris Cedex 15, France. synthesis of prostaglandin E z (PGE2); however the total amount of PGE 2 synthesized in the latter case was significantly lower than that ob- served with viable organisms. Our results suggest that the inability of human macrophages to con- trol M. ar,ium infection is linked to immunosup- pressive pathways, e.g. enhanced synthesis of PGE 2 and also to an impairment of normal mi- crobicidal functions of the infected macrophages. 2. INTRODUCTION Mycobacterium ac'ium complex (MAC) is one of the most prevalent pathogens among oppor- tunist infections in AIDS patients [1]. In addition, MAC infections in persons without predisposing conditions are becoming an important clinical problem [2]. Clinical management of these infec- tions is made difficult by the fact that MAC organisms are resistant to antimycobacterial Downloaded from https://academic.oup.com/femspd/article-abstract/4/5/273/2911787 by guest on 29 May 2020