RICK promotes inflammation and lethality after gram-negative bacterial infection in mice stimulated with lipopolysaccharide

Jong Hwan Park, Yungi Kim, Gabriel Núñez

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

RICK (receptor-interacting protein-like interacting caspase-like apoptosis regulatory protein kinase), a serine-threonine kinase, functions downstream of the pattern recognition receptors Nod1 and Nod2 to mediate NF-κB and mitogen-activated protein kinase (MAPK) activation in response to specific microbial stimuli. However, the function of RICK in the recognition and host defense of gram-negative bacteria remains poorly understood. We report here that infection of wild-type and RICK-deficient macrophages with Pseudomonas aeruginosa and Escherichia coli elicited comparable activation of NF-κB and MAPKs as well as secretion of proinflammatory cytokines. However, production of interleukin 6 (IL-6) and IL-1p induced by these gram- negative bacteria was impaired in RICK-deficient macrophages when the cells had previously been stimulated with lipopolysaccharide (LPS) or E. coli. The diminished proinflammatory response of RICK-deficient macrophages to bacteria was associated with reduced activation of NF-κB and MAPKs. Importantly, mutant mice deficient in RICK were less susceptible than wild-type mice to P. aeruginosa infection when the animals had previously been stimulated with LPS. The reduced lethality of RICK-deficient mice infected with P. aeruginosa was independent of pathogen clearance but was associated with diminished production of proinflammatory molecules in vivo. These results demonstrate that RICK contributes to the induction of proinflammatory responses and susceptibility to gram-negative bacteria after exposure to LPS, a condition that is associated with reduced Toll-like receptor signaling.

Original languageEnglish
Pages (from-to)1569-1578
Number of pages10
JournalInfection and Immunity
Volume77
Issue number4
DOIs
Publication statusPublished - 2009 Apr
Externally publishedYes

Fingerprint

Gram-Negative Bacterial Infections
Gram-Negative Bacteria
Pseudomonas aeruginosa
Lipopolysaccharides
Macrophages
Inflammation
Receptor-Interacting Protein Serine-Threonine Kinases
Escherichia coli
Pattern Recognition Receptors
Pseudomonas Infections
Apoptosis Regulatory Proteins
Toll-Like Receptors
Protein-Serine-Threonine Kinases
Caspases
Mitogen-Activated Protein Kinases
Protein Kinases
Interleukin-6
Cytokines
Bacteria
Infection

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

RICK promotes inflammation and lethality after gram-negative bacterial infection in mice stimulated with lipopolysaccharide. / Park, Jong Hwan; Kim, Yungi; Núñez, Gabriel.

In: Infection and Immunity, Vol. 77, No. 4, 04.2009, p. 1569-1578.

Research output: Contribution to journalArticle

@article{24b21a740b7840bdba9d83c25b52d9e7,
title = "RICK promotes inflammation and lethality after gram-negative bacterial infection in mice stimulated with lipopolysaccharide",
abstract = "RICK (receptor-interacting protein-like interacting caspase-like apoptosis regulatory protein kinase), a serine-threonine kinase, functions downstream of the pattern recognition receptors Nod1 and Nod2 to mediate NF-κB and mitogen-activated protein kinase (MAPK) activation in response to specific microbial stimuli. However, the function of RICK in the recognition and host defense of gram-negative bacteria remains poorly understood. We report here that infection of wild-type and RICK-deficient macrophages with Pseudomonas aeruginosa and Escherichia coli elicited comparable activation of NF-κB and MAPKs as well as secretion of proinflammatory cytokines. However, production of interleukin 6 (IL-6) and IL-1p induced by these gram- negative bacteria was impaired in RICK-deficient macrophages when the cells had previously been stimulated with lipopolysaccharide (LPS) or E. coli. The diminished proinflammatory response of RICK-deficient macrophages to bacteria was associated with reduced activation of NF-κB and MAPKs. Importantly, mutant mice deficient in RICK were less susceptible than wild-type mice to P. aeruginosa infection when the animals had previously been stimulated with LPS. The reduced lethality of RICK-deficient mice infected with P. aeruginosa was independent of pathogen clearance but was associated with diminished production of proinflammatory molecules in vivo. These results demonstrate that RICK contributes to the induction of proinflammatory responses and susceptibility to gram-negative bacteria after exposure to LPS, a condition that is associated with reduced Toll-like receptor signaling.",
author = "Park, {Jong Hwan} and Yungi Kim and Gabriel N{\'u}{\~n}ez",
year = "2009",
month = "4",
doi = "10.1128/IAI.01505-08",
language = "English",
volume = "77",
pages = "1569--1578",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "4",

}

TY - JOUR

T1 - RICK promotes inflammation and lethality after gram-negative bacterial infection in mice stimulated with lipopolysaccharide

AU - Park, Jong Hwan

AU - Kim, Yungi

AU - Núñez, Gabriel

PY - 2009/4

Y1 - 2009/4

N2 - RICK (receptor-interacting protein-like interacting caspase-like apoptosis regulatory protein kinase), a serine-threonine kinase, functions downstream of the pattern recognition receptors Nod1 and Nod2 to mediate NF-κB and mitogen-activated protein kinase (MAPK) activation in response to specific microbial stimuli. However, the function of RICK in the recognition and host defense of gram-negative bacteria remains poorly understood. We report here that infection of wild-type and RICK-deficient macrophages with Pseudomonas aeruginosa and Escherichia coli elicited comparable activation of NF-κB and MAPKs as well as secretion of proinflammatory cytokines. However, production of interleukin 6 (IL-6) and IL-1p induced by these gram- negative bacteria was impaired in RICK-deficient macrophages when the cells had previously been stimulated with lipopolysaccharide (LPS) or E. coli. The diminished proinflammatory response of RICK-deficient macrophages to bacteria was associated with reduced activation of NF-κB and MAPKs. Importantly, mutant mice deficient in RICK were less susceptible than wild-type mice to P. aeruginosa infection when the animals had previously been stimulated with LPS. The reduced lethality of RICK-deficient mice infected with P. aeruginosa was independent of pathogen clearance but was associated with diminished production of proinflammatory molecules in vivo. These results demonstrate that RICK contributes to the induction of proinflammatory responses and susceptibility to gram-negative bacteria after exposure to LPS, a condition that is associated with reduced Toll-like receptor signaling.

AB - RICK (receptor-interacting protein-like interacting caspase-like apoptosis regulatory protein kinase), a serine-threonine kinase, functions downstream of the pattern recognition receptors Nod1 and Nod2 to mediate NF-κB and mitogen-activated protein kinase (MAPK) activation in response to specific microbial stimuli. However, the function of RICK in the recognition and host defense of gram-negative bacteria remains poorly understood. We report here that infection of wild-type and RICK-deficient macrophages with Pseudomonas aeruginosa and Escherichia coli elicited comparable activation of NF-κB and MAPKs as well as secretion of proinflammatory cytokines. However, production of interleukin 6 (IL-6) and IL-1p induced by these gram- negative bacteria was impaired in RICK-deficient macrophages when the cells had previously been stimulated with lipopolysaccharide (LPS) or E. coli. The diminished proinflammatory response of RICK-deficient macrophages to bacteria was associated with reduced activation of NF-κB and MAPKs. Importantly, mutant mice deficient in RICK were less susceptible than wild-type mice to P. aeruginosa infection when the animals had previously been stimulated with LPS. The reduced lethality of RICK-deficient mice infected with P. aeruginosa was independent of pathogen clearance but was associated with diminished production of proinflammatory molecules in vivo. These results demonstrate that RICK contributes to the induction of proinflammatory responses and susceptibility to gram-negative bacteria after exposure to LPS, a condition that is associated with reduced Toll-like receptor signaling.

UR - http://www.scopus.com/inward/record.url?scp=63149147333&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=63149147333&partnerID=8YFLogxK

U2 - 10.1128/IAI.01505-08

DO - 10.1128/IAI.01505-08

M3 - Article

C2 - 19188356

AN - SCOPUS:63149147333

VL - 77

SP - 1569

EP - 1578

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 4

ER -