Project at a glance

Dictyostelium amoebae: a genetic model to study phagocytosis and host-pathogen interactions

Phagocytosis is the process by which phagocytic cells ingest big particles such as bacteria. Phagocytic cells like macrophages are an essential element in the defense of our body against invading microorganisms. To dissect phagocytosis at the molecular level, we are making use of a phagocytic cell amenable to genetic analysis, the amoeba Dictyostelium discoideum. Amoebae phagocytose bacteria to feed upon them, and the molecular mechanisms involved are very similar to those observed in mammalian phagocytic cells.

Using this system, we have isolated and characterized a number of gene products implicated at various stages in phagocytosis, or in other steps of the endocytic pathway. These studies either lead to identification of new genes involved in these processes, or they shed new light on the function of known gene products, through detailed analysis of specific knockout cells. The same system was also used to study how bacteria are killed following phagocytosis, based on the analysis of Dictyostelium mutants defective for intracellular killing. Our results indicate that different mechanisms are involved in the killing of various classes of bacteria. Finally, certain pathogenic bacteria (e.g. Pseudomonas aeruginosa) can escape phagocytic cells making use of various virulence strategies. We have used Dictyostelium amoebae as a system to analyze these virulence mechanisms.

These various themes (phagocytosis, endocytosis, intracellular killing, pathogenic bacteria) are intimately linked both conceptually and at the experimental level. Our results demonstrate that Dictyostelium can be a simple and powerful system to analyze the complex relationships between phagocytic cells and bacteria.