Host-pathogen interactions

Dictyostelium is an amoeba that normally lives in soil surviving by hunting down and eating bacteria by phagocytosis. In many respects this is similar to the role of immune cells such as neutrophils and macrophages, which are the body’s first line of defence against invading pathogens. These phagocytes are also often the first cells to be infected as many pathogens have evolved a number of tricks to avoid being eaten.

Dictyostelium amoebae eating GFP and pHrodo labelled bacteria which turn from green to red when killed. The mechanisms underlying this are highly similar to those of immune cells.

Dictyostelium provides an excellent model system in which to study how pathogens interact with their host, and circumvents many of the experimental difficulties and limitations of working with macrophages and neutrophils. Many opportunistic human pathogens also normally live in the soil, and only infect those who are immunocompromised. These pathogens have therefore primarily evolved to avoid predatory amoeba such as Dictyostelium and Acanthamoeba rather than human immune cells.

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Cryptococcus neoformans (Red) after phagocytosis by Dictyostelium.

In collaboration with the Hagedorn, Soldati and Johnson labs we are applying our knowledge of autophagy, macropinocytosis, Dictyostelium cell biology and trafficking to studies of mycobacterium and cryptococcosis infection.

Recruitment of the autophagic machinery to mycobacterium as they are expelled out of Dictyostelium. From Gerstenmeier and Pilla et al. PNAS 2015

University of Sheffield