Department of Microbiology Papers

Document Type

Journal Article

Date of this Version

6-12-2009

Publication Source

PLoS Pathogens

Volume

5

Issue

6

Start Page

e1000478

DOI

10.1371/journal.ppat.1000478

Abstract

Dendritic cells (DCs) are specialized phagocytes that internalize exogenous antigens and microbes at peripheral sites, and then migrate to lymphatic organs to display foreign peptides to naïve T cells. There are several examples where DCs have been shown to be more efficient at restricting the intracellular replication of pathogens compared to macrophages, a property that could prevent DCs from enhancing pathogen dissemination. To understand DC responses to pathogens, we investigated the mechanisms by which mouse DCs are able to restrict replication of the intracellular pathogen Legionella pneumophila. We show that both DCs and macrophages have the ability to interfere with L. pneumophila replication through a cell death pathway mediated by caspase-1 and Naip5. L. pneumophila that avoided Naip5-dependent responses, however, showed robust replication in macrophages but remained unable to replicate in DCs. Apoptotic cell death mediated by caspase-3 was found to occur much earlier in DCs following infection by L. pneumophila compared to macrophages infected similarly. Eliminating the pro-apoptotic proteins Bax and Bak or overproducing the anti-apoptotic protein Bcl-2 were both found to restore L. pneumophila replication in DCs. Thus, DCs have a microbial response pathway that rapidly activates apoptosis to limit pathogen replication.

Copyright/Permission Statement

This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Comments

At the time of publication, author Sunny Shin was affiliated with Yale University School of Medicine. Currently, she is a faculty member at the Perelman School of Medicine at the University of Pennsylvania.

Keywords

Legionella pneumophila, apoptosis, macrophages, bacterial pathogens, intracellular pathogens, vacuoles, cell death, alleles

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Date Posted: 17 June 2015

This document has been peer reviewed.