Innate killing of Leishmania donovani by macrophages of the splenic marginal zone requires IRF-7.

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.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Phillips R,Svensson M,Aziz N,Maroof A,Brown N,Beattie L,Signoret N,Kaye PM

doi

10.1371/journal.ppat.1000813

subject

Has Abstract

pub_date

2010-03-12 00:00:00

pages

e1000813

issue

3

eissn

1553-7366

issn

1553-7374

journal_volume

6

pub_type

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