MONOCYTES OF INDIVIDUAL HUMAN-SUBJECTS DISPLAY HETEROGENEOUS BACTERIAL UPTAKE AND ANTILISTERIAL ACTIVITY

Peripheral blood monocytes (Mo) of normal human donors simultaneously exhibit two subsets differing in their functional activity towards the facultative intracellular bacterium Listeria monocytogenes. One subse t (on average, 25% of total Mo) was characteristically able to ingest a large number of L. monocytogenes bacteria and permitted intracellula r growth of these bacteria. The other Mo subpopulation (on average, 75 % of total Mo) was far less active in phagocytosing L. monocytogenes a nd restricted intracellular L. monocytogenes growth. Electron microsco py revealed that the Listeria-permissive Mo subset allowed the bacteri a to escape to the cytosol, a mechanism by which these bacteria evade the lethal attack of phagocytes. The Listeria-restrictive Mo subset, o n the other hand, confined the bacteria to the phagolysosomes, where t hey were exposed to the killing mechanisms of the Mo. Permissiveness f or L. monocytogenes growth was further associated with differences in the capacity of the Mo subsets to synthesize tumor necrosis factor alp ha (TNF-alpha), an important mediator in the defense against intracell ular bacteria. Following challenge with L. monocytogenes, the Listeria -restrictive Mo subset secreted two to six times more TNF-alpha than d id the Listeria-permissive Mo subset. Enhanced TNF-alpha secretion was paralleled by increased accumulation of TNF-alpha mRNA as assessed by quantitative PCR. Despite these functional differences, the two Mo su bsets were indistinguishable with respect to expression of cell surfac e markers known to be involved in adherence and phagocytosis of microb es. A speculative physiological role of the two Mo subsets may lie in the dual function of Mo as microbicidal effector cells and accessory c ells for antigen-specific immune reactions.