RRC ID 11783
Author Phillips R, Svensson M, Aziz N, Maroof A, Brown N, Beattie L, Signoret N, Kaye PM.
Title Innate killing of Leishmania donovani by macrophages of the splenic marginal zone requires IRF-7.
Journal PLoS Pathog.
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.
Volume 6(3)
Pages e1000813
Published 2010-3-12
DOI 10.1371/journal.ppat.1000813
PMID 20300600
PMC PMC2837405
MeSH Animals Gene Expression / immunology Interferon Regulatory Factor-7 / genetics Interferon Regulatory Factor-7 / immunology* Interferon Regulatory Factor-7 / metabolism Interferon-alpha / immunology Interferon-alpha / metabolism Interferon-gamma / immunology Interferon-gamma / metabolism Leishmania donovani / immunology* Leishmaniasis, Visceral / immunology* Macrophages / cytology Macrophages / immunology* Macrophages / parasitology* Mice Mice, Inbred C57BL Nitric Oxide / metabolism Phagosomes / immunology RNA, Small Interfering Spleen / immunology Spleen / parasitology
IF 6.158
Times Cited 34
Mice IRF-7 knockout mice C57BL/6J