Department of Microbiology Papers

Document Type

Journal Article

Date of this Version

11-28-2008

Publication Source

PLoS Pathogens

Volume

4

Issue

11

Start Page

e1000220

DOI

10.1371/journal.ppat.1000220

Abstract

The immune system must discriminate between pathogenic and nonpathogenic microbes in order to initiate an appropriate response. Toll-like receptors (TLRs) detect microbial components common to both pathogenic and nonpathogenic bacteria, whereas Nod-like receptors (NLRs) sense microbial components introduced into the host cytosol by the specialized secretion systems or pore-forming toxins of bacterial pathogens. The host signaling pathways that respond to bacterial secretion systems remain poorly understood. Infection with the pathogen Legionella pneumophila, which utilizes a type IV secretion system (T4SS), induced an increased proinflammatory cytokine response compared to avirulent bacteria in which the T4SS was inactivated. This enhanced response involved NF-κB activation by TLR signaling as well as Nod1 and Nod2 detection of type IV secretion. Furthermore, a TLR- and RIP2-independent pathway leading to p38 and SAPK/JNK MAPK activation was found to play an equally important role in the host response to virulent L. pneumophila. Activation of this MAPK pathway was T4SS-dependent and coordinated with TLR signaling to mount a robust proinflammatory cytokine response to virulent L. pneumophila. These findings define a previously uncharacterized host response to bacterial type IV secretion that activates MAPK signaling and demonstrate that coincident detection of multiple bacterial components enables immune discrimination between virulent and avirulent bacteria.

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, macrophages, MAPK signaling cascades, cytokines, bacterial pathogens, DNA transcription, immune receptor signaling, immune response

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Date Posted: 17 June 2015

This document has been peer reviewed.