Differential uptake and killing potential of Campylobacter jejuni by human peripheral monocytes/macrophages

Abstract

The ability of Campylobacter jejuni to survive in monocytes after phagocytic uptake was tested in a new in vitro model using adherent macrophages derived from human peripheral monocytes. The cells were stimulated with cytokines before use to ensure full phagocytic and killing activity. The kinetics of uptake and killing of bacteria was followed for 72 h with 16 strains, including stool and blood isolates and laboratory adapted strains. Significant bacterial strain differences were not observed, but the viability of phagocytosed bacteria was dependent on the individual donating the macrophages. The majority of blood donors carried macrophages that killed phagocytosed Campylobacter within 24 or 48 h. There was no correlation between the source of isolation of the strains and relative intracellular survival. Bacterial mutants of superoxide dismutase, catalase or polyphosphate kinase were all as sensitive to macrophage killing as their isogenic wild-type strain. In contrast, about 10% of the voluntary blood donors carried monocytes which were incapable of killing phagocytosed bacteria. Such macrophages displayed normal uptake, but killing was insufficient and bacterial growth was observed with all strains and mutants tested. We conclude that (1) since in most cases activated human macrophages kill C. jejuni efficiently after phagocytosis, intra-phagocytic survival is not a common phenomenon during Campylobacter infection; and (2) those individuals carrying macrophages that are unable to destroy phagocytosed bacteria are at risk to develop a bacteremia during Campylobacter infection.