The Cytosolic Sensors Nod1 and Nod2 Are Critical for Bacterial Recognition and Host Defense after Exposure to Toll-like Receptor Ligands

Yungi Kim, Jong Hwan Park, Michael H. Shaw, Luigi Franchi, Naohiro Inohara, Gabriel Núñez

Research output: Contribution to journalArticle

195 Citations (Scopus)

Abstract

The cytosolic sensors Nod1 and Nod2 and Toll-like receptors (TLRs) activate defense signaling pathways in response to microbial stimuli. However, the role of Nod1 and Nod2 and their interplay with TLRs during systemic bacterial infection remains poorly understood. Here, we report that macrophages or mice made insensitive to TLRs by previous exposure to microbial ligands remained responsive to Nod1 and Nod2 stimulation. Furthermore, Nod1- and Nod2-mediated signaling and gene expression are enhanced in TLR-tolerant macrophages. Further analyses revealed that innate immune responses induced by bacterial infection relied on Nod1 and Nod2 and their adaptor RICK in macrophages pretreated with TLR ligands but not in naive macrophages. In addition, bacterial clearance upon systemic infection with L. monocytogenes was critically dependent on Nod1 and Nod2 when mice were previously stimulated with lipopolysaccharide or E. coli. Thus, Nod1 and Nod2 are important for microbial recognition and host defense after TLR stimulation.

Original languageEnglish
Pages (from-to)246-257
Number of pages12
JournalImmunity
Volume28
Issue number2
DOIs
Publication statusPublished - 2008 Feb 15
Externally publishedYes

Fingerprint

Toll-Like Receptors
Ligands
Macrophages
Bacterial Infections
Innate Immunity
Lipopolysaccharides
Escherichia coli
Gene Expression
Infection

Keywords

  • CELLIMMUNO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

The Cytosolic Sensors Nod1 and Nod2 Are Critical for Bacterial Recognition and Host Defense after Exposure to Toll-like Receptor Ligands. / Kim, Yungi; Park, Jong Hwan; Shaw, Michael H.; Franchi, Luigi; Inohara, Naohiro; Núñez, Gabriel.

In: Immunity, Vol. 28, No. 2, 15.02.2008, p. 246-257.

Research output: Contribution to journalArticle

Kim, Yungi ; Park, Jong Hwan ; Shaw, Michael H. ; Franchi, Luigi ; Inohara, Naohiro ; Núñez, Gabriel. / The Cytosolic Sensors Nod1 and Nod2 Are Critical for Bacterial Recognition and Host Defense after Exposure to Toll-like Receptor Ligands. In: Immunity. 2008 ; Vol. 28, No. 2. pp. 246-257.
@article{236e1f7e60be4980a6b6513b9c8106dc,
title = "The Cytosolic Sensors Nod1 and Nod2 Are Critical for Bacterial Recognition and Host Defense after Exposure to Toll-like Receptor Ligands",
abstract = "The cytosolic sensors Nod1 and Nod2 and Toll-like receptors (TLRs) activate defense signaling pathways in response to microbial stimuli. However, the role of Nod1 and Nod2 and their interplay with TLRs during systemic bacterial infection remains poorly understood. Here, we report that macrophages or mice made insensitive to TLRs by previous exposure to microbial ligands remained responsive to Nod1 and Nod2 stimulation. Furthermore, Nod1- and Nod2-mediated signaling and gene expression are enhanced in TLR-tolerant macrophages. Further analyses revealed that innate immune responses induced by bacterial infection relied on Nod1 and Nod2 and their adaptor RICK in macrophages pretreated with TLR ligands but not in naive macrophages. In addition, bacterial clearance upon systemic infection with L. monocytogenes was critically dependent on Nod1 and Nod2 when mice were previously stimulated with lipopolysaccharide or E. coli. Thus, Nod1 and Nod2 are important for microbial recognition and host defense after TLR stimulation.",
keywords = "CELLIMMUNO, MOLIMMUNO",
author = "Yungi Kim and Park, {Jong Hwan} and Shaw, {Michael H.} and Luigi Franchi and Naohiro Inohara and Gabriel N{\'u}{\~n}ez",
year = "2008",
month = "2",
day = "15",
doi = "10.1016/j.immuni.2007.12.012",
language = "English",
volume = "28",
pages = "246--257",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - The Cytosolic Sensors Nod1 and Nod2 Are Critical for Bacterial Recognition and Host Defense after Exposure to Toll-like Receptor Ligands

AU - Kim, Yungi

AU - Park, Jong Hwan

AU - Shaw, Michael H.

AU - Franchi, Luigi

AU - Inohara, Naohiro

AU - Núñez, Gabriel

PY - 2008/2/15

Y1 - 2008/2/15

N2 - The cytosolic sensors Nod1 and Nod2 and Toll-like receptors (TLRs) activate defense signaling pathways in response to microbial stimuli. However, the role of Nod1 and Nod2 and their interplay with TLRs during systemic bacterial infection remains poorly understood. Here, we report that macrophages or mice made insensitive to TLRs by previous exposure to microbial ligands remained responsive to Nod1 and Nod2 stimulation. Furthermore, Nod1- and Nod2-mediated signaling and gene expression are enhanced in TLR-tolerant macrophages. Further analyses revealed that innate immune responses induced by bacterial infection relied on Nod1 and Nod2 and their adaptor RICK in macrophages pretreated with TLR ligands but not in naive macrophages. In addition, bacterial clearance upon systemic infection with L. monocytogenes was critically dependent on Nod1 and Nod2 when mice were previously stimulated with lipopolysaccharide or E. coli. Thus, Nod1 and Nod2 are important for microbial recognition and host defense after TLR stimulation.

AB - The cytosolic sensors Nod1 and Nod2 and Toll-like receptors (TLRs) activate defense signaling pathways in response to microbial stimuli. However, the role of Nod1 and Nod2 and their interplay with TLRs during systemic bacterial infection remains poorly understood. Here, we report that macrophages or mice made insensitive to TLRs by previous exposure to microbial ligands remained responsive to Nod1 and Nod2 stimulation. Furthermore, Nod1- and Nod2-mediated signaling and gene expression are enhanced in TLR-tolerant macrophages. Further analyses revealed that innate immune responses induced by bacterial infection relied on Nod1 and Nod2 and their adaptor RICK in macrophages pretreated with TLR ligands but not in naive macrophages. In addition, bacterial clearance upon systemic infection with L. monocytogenes was critically dependent on Nod1 and Nod2 when mice were previously stimulated with lipopolysaccharide or E. coli. Thus, Nod1 and Nod2 are important for microbial recognition and host defense after TLR stimulation.

KW - CELLIMMUNO

KW - MOLIMMUNO

UR - http://www.scopus.com/inward/record.url?scp=39149094587&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39149094587&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2007.12.012

DO - 10.1016/j.immuni.2007.12.012

M3 - Article

C2 - 18261938

AN - SCOPUS:39149094587

VL - 28

SP - 246

EP - 257

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 2

ER -