RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs

Jong Hwan Park, Yungi Kim, Christine McDonald, Thirumala Devi Kanneganti, Mizuho Hasegawa, Mathilde Body-Malapel, Naohiro Inohara, Gabriel Núñez

Research output: Contribution to journalArticle

307 Citations (Scopus)

Abstract

RICK is a kinase that has been implicated in Nod1 and Nod2 signaling. In addition, RICK has been proposed to mediate TLR signaling in that its absence confers reduced responses to certain bacterial products such as LPS. We show here that macrophages and mice lacking RICK are defective in their responses to Nod1 and Nod2 agonists but exhibit unimpaired responses to synthetic and highly purified TLR agonists. Furthermore, production of chemokines induced by the bacterial dipeptide γ-D-glutamyl-meso-diaminopimelic acid was intact in MyD88 deficient mice but abolished in RICK-null mice. Stimulation of macrophages with muramyl dipeptide, the Nod2 activator, enhanced immune responses induced by LPS, IFN-γ, and heat-killed Listeria in wild-type but not in RICK- or Nod2-deficient macrophages. Finally, we show that the absence of RICK or double deficiency of Nod1 and Nod2 was associated with reduced cytokine production in Listeria-infected macrophages. These results demonstrate that RICK functions in innate immunity by mediating Nod1 and Nod2 signaling but not TLR-mediated immune responses.

Original languageEnglish
Pages (from-to)2380-2386
Number of pages7
JournalJournal of Immunology
Volume178
Issue number4
Publication statusPublished - 2007 Feb 15
Externally publishedYes

Fingerprint

Innate Immunity
Macrophages
Listeria
Acetylmuramyl-Alanyl-Isoglutamine
Diaminopimelic Acid
Dipeptides
Chemokines
Phosphotransferases
Hot Temperature
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

Park, J. H., Kim, Y., McDonald, C., Kanneganti, T. D., Hasegawa, M., Body-Malapel, M., ... Núñez, G. (2007). RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs. Journal of Immunology, 178(4), 2380-2386.

RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs. / Park, Jong Hwan; Kim, Yungi; McDonald, Christine; Kanneganti, Thirumala Devi; Hasegawa, Mizuho; Body-Malapel, Mathilde; Inohara, Naohiro; Núñez, Gabriel.

In: Journal of Immunology, Vol. 178, No. 4, 15.02.2007, p. 2380-2386.

Research output: Contribution to journalArticle

Park, JH, Kim, Y, McDonald, C, Kanneganti, TD, Hasegawa, M, Body-Malapel, M, Inohara, N & Núñez, G 2007, 'RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs', Journal of Immunology, vol. 178, no. 4, pp. 2380-2386.
Park JH, Kim Y, McDonald C, Kanneganti TD, Hasegawa M, Body-Malapel M et al. RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs. Journal of Immunology. 2007 Feb 15;178(4):2380-2386.
Park, Jong Hwan ; Kim, Yungi ; McDonald, Christine ; Kanneganti, Thirumala Devi ; Hasegawa, Mizuho ; Body-Malapel, Mathilde ; Inohara, Naohiro ; Núñez, Gabriel. / RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs. In: Journal of Immunology. 2007 ; Vol. 178, No. 4. pp. 2380-2386.
@article{af2cf19080714b62a9f701c33ad5bf55,
title = "RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs",
abstract = "RICK is a kinase that has been implicated in Nod1 and Nod2 signaling. In addition, RICK has been proposed to mediate TLR signaling in that its absence confers reduced responses to certain bacterial products such as LPS. We show here that macrophages and mice lacking RICK are defective in their responses to Nod1 and Nod2 agonists but exhibit unimpaired responses to synthetic and highly purified TLR agonists. Furthermore, production of chemokines induced by the bacterial dipeptide γ-D-glutamyl-meso-diaminopimelic acid was intact in MyD88 deficient mice but abolished in RICK-null mice. Stimulation of macrophages with muramyl dipeptide, the Nod2 activator, enhanced immune responses induced by LPS, IFN-γ, and heat-killed Listeria in wild-type but not in RICK- or Nod2-deficient macrophages. Finally, we show that the absence of RICK or double deficiency of Nod1 and Nod2 was associated with reduced cytokine production in Listeria-infected macrophages. These results demonstrate that RICK functions in innate immunity by mediating Nod1 and Nod2 signaling but not TLR-mediated immune responses.",
author = "Park, {Jong Hwan} and Yungi Kim and Christine McDonald and Kanneganti, {Thirumala Devi} and Mizuho Hasegawa and Mathilde Body-Malapel and Naohiro Inohara and Gabriel N{\'u}{\~n}ez",
year = "2007",
month = "2",
day = "15",
language = "English",
volume = "178",
pages = "2380--2386",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "4",

}

TY - JOUR

T1 - RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs

AU - Park, Jong Hwan

AU - Kim, Yungi

AU - McDonald, Christine

AU - Kanneganti, Thirumala Devi

AU - Hasegawa, Mizuho

AU - Body-Malapel, Mathilde

AU - Inohara, Naohiro

AU - Núñez, Gabriel

PY - 2007/2/15

Y1 - 2007/2/15

N2 - RICK is a kinase that has been implicated in Nod1 and Nod2 signaling. In addition, RICK has been proposed to mediate TLR signaling in that its absence confers reduced responses to certain bacterial products such as LPS. We show here that macrophages and mice lacking RICK are defective in their responses to Nod1 and Nod2 agonists but exhibit unimpaired responses to synthetic and highly purified TLR agonists. Furthermore, production of chemokines induced by the bacterial dipeptide γ-D-glutamyl-meso-diaminopimelic acid was intact in MyD88 deficient mice but abolished in RICK-null mice. Stimulation of macrophages with muramyl dipeptide, the Nod2 activator, enhanced immune responses induced by LPS, IFN-γ, and heat-killed Listeria in wild-type but not in RICK- or Nod2-deficient macrophages. Finally, we show that the absence of RICK or double deficiency of Nod1 and Nod2 was associated with reduced cytokine production in Listeria-infected macrophages. These results demonstrate that RICK functions in innate immunity by mediating Nod1 and Nod2 signaling but not TLR-mediated immune responses.

AB - RICK is a kinase that has been implicated in Nod1 and Nod2 signaling. In addition, RICK has been proposed to mediate TLR signaling in that its absence confers reduced responses to certain bacterial products such as LPS. We show here that macrophages and mice lacking RICK are defective in their responses to Nod1 and Nod2 agonists but exhibit unimpaired responses to synthetic and highly purified TLR agonists. Furthermore, production of chemokines induced by the bacterial dipeptide γ-D-glutamyl-meso-diaminopimelic acid was intact in MyD88 deficient mice but abolished in RICK-null mice. Stimulation of macrophages with muramyl dipeptide, the Nod2 activator, enhanced immune responses induced by LPS, IFN-γ, and heat-killed Listeria in wild-type but not in RICK- or Nod2-deficient macrophages. Finally, we show that the absence of RICK or double deficiency of Nod1 and Nod2 was associated with reduced cytokine production in Listeria-infected macrophages. These results demonstrate that RICK functions in innate immunity by mediating Nod1 and Nod2 signaling but not TLR-mediated immune responses.

UR - http://www.scopus.com/inward/record.url?scp=33846936219&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846936219&partnerID=8YFLogxK

M3 - Article

VL - 178

SP - 2380

EP - 2386

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 4

ER -