Innate Killing of Leishmania donovani by Macrophages of the Splenic Marginal Zone Requires IRF-7 |
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| Authors: | Rebecca Phillips Mattias Svensson Naveed Aziz Asher Maroof Najmeeyah Brown Lynette Beattie Nathalie Signoret Paul M Kaye |
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| Institution: | 1. Centre for Immunology and Infection, Hull York Medical School and Department of Biology, University of York, York, United Kingdom.; 2. Center for Infectious Medicine, Department of Medicine, F59, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.; 3. The Technology Facility, Department of Biology, University of York, York, United Kingdom.;Imperial College London, United Kingdom |
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| Abstract: | Highly phagocytic macrophages line the marginal zone (MZ) of the spleen and the lymph node subcapsular sinus. Although these macrophages have been attributed with a variety of functions, including the uptake and clearance of blood and lymph-borne pathogens, little is known about the effector mechanisms they employ after pathogen uptake. Here, we have combined gene expression profiling and RNAi using a stromal macrophage cell line with in situ analysis of the leishmanicidal activity of marginal zone macrophages (MZM) and marginal metallophilic macrophages (MMM) in wild type and gene targeted mice. Our data demonstrate a critical role for interferon regulatory factor-7 (IRF-7) in regulating the killing of intracellular Leishmania donovani by these specialised splenic macrophage sub-populations. This study, therefore, identifies a new role for IRF-7 as a regulator of innate microbicidal activity against this, and perhaps other, non-viral intracellular pathogens. This study also highlights the importance of selecting appropriate macrophage populations when studying pathogen interactions with this functionally diverse lineage of cells. |
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