236A Poster - 02. Immunity and the microbiome
Thursday April 07, 2:00 PM - 4:00 PM

Identification and characterisation of functionally distinct macrophage subpopulations in Drosophila


Authors:
Martin Zeidler 1; Jonathon Coates 1,2,3; Elliot Brooks 2; Amy Brittle 2; Emma Armitage 2; Iwan Evans 2

Affiliations:
1) The Bateson Centre, School of Biosciences, University of Sheffield, Sheffield, United Kingdom.; 2) Department of Infection, Immunity and Cardiovascular Disease and the Bateson Centre, University of Sheffield, Sheffield, United Kingdom.; 3) Current address: William Harvey Research Institute, QMUL, London, United Kingdom

Keywords:
a. cellular immunity; t. mesodermal derivatives

Drosophila blood is dominated by a macrophage-like lineage of cells termed plasmatocytes which differentiate in two waves during embryonic and L3 larval development and are maintained throughout adult life. Throughout this time, plasmatocytes fulfil multiple roles, including wound responses, clearance of apoptotic debris and the provision of an innate immune response to infection. However, until very recently, the plasmatocyte lineage was thought to represent a homogeneous population – a stark contrast to vertebrate macrophages which assume a range of diverse functional and gene expression states.

Here we present our identification of a number of enhancer elements labelling plasmatocyte subpopulations, which we show to vary in abundance across development. We show that some of these subpopulations exhibit functional differences compared to the overall blood cell population, including more potent responses to wounds, altered apoptotic cell clearance and differential localisation / dynamics in pupae and adults. Genes located adjacent to enhancers showing altered plasmatocyte behaviour include Calnexin14D, which, when over expressed in all plasmatocytes, improves wound responses, causing the overall population to more closely resemble the marked subpopulation. These results suggest that differential gene expression not only labels, but also drives changes in subset behaviour. Finally, we show that exposure to increased levels of apoptotic cell death is sufficient to modulate the number of cells within certain subpopulations – further suggesting that subpopulations are dynamic and respond to environmental cues and stresses.

Taken together, our work demonstrates a degree of adaptive and functional macrophage heterogeneity in Drosophila that has not previously been described. It has identified mechanisms involved in subpopulation specification and function and provides a starting point for future studies into functional in vivo Drosophilamacrophage heterogeneity.