Cyclic Nucleotides and Phagosome-Lysosome Fusion in Mouse Peritoneal Macrophages

Abstract

In vitro studies have shown that several of the species of pathogenic micro-organism that can survive and multiply inside macrophages remain within phagosomes and avoid exposure to lysosomal enzymes by either failing to elicit or inhibiting phagosome-lysosome fusion. These organisms include Mycobacterium tuberculosis (Armstrong & Hart 1971), Toxoplasma gondii (Jones & Hirsch 1972), Mycobacterium microti (Hart et al. 1972) and Chlamydia species (Friis 1972; Lawn et al. 1973; Todd & Storz 1975; Wyrick & Brownridge 1978). Evasion of lysosomal enzymes would be expected to contribute to the success of these intracellular parasites. Indeed, when phagosome-lysosome fusion was induced by pre-coating the organisms with antibody before ingestion, T. gondii and Chlamydia psittaci were destroyed (Jones et al. 1975; Anderson et al. 1976; Wyrick et al. 1978) although M. tuberculosis was not (Armstrong & Hart 19 75). We have proposed that such organisms might normally ’switch off phagosome-lysosome fusion by causing an increase in cyclic adenosine 3′,5′-monophosphate (cyclic AMP) in infected macrophages (Lowrie et al. 1975).