Characterization of NLRP12 during the In Vivo Host Immune Response to Klebsiella pneumoniae and Mycobacterium tuberculosis

Irving C. Allen, Erin McElvania-TeKippe, Justin E. Wilson, John D. Lich, Janelle C. Arthur, Jonathan T. Sullivan, Miriam Braunstein, Jenny P Y Ting

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The majority of nucleotide binding domain leucine rich repeats-containing (NLR) family members has yet to be functionally characterized. Of the described NLRs, most are considered to be proinflammatory and facilitate IL-1β production. However, a newly defined sub-group of NLRs that function as negative regulators of inflammation have been identified based on their abilities to attenuate NF-κB signaling. NLRP12 (Monarch-1) is a prototypical member of this sub-group that negatively regulates both canonical and noncanonical NF-κB signaling in biochemical assays and in colitis and colon cancer models. The role of NLRP12 in infectious diseases has not been extensively studied. Here, we characterized the innate immune response of Nlrp12-/- mice following airway exposure to LPS, Klebsiella pneumoniae and Mycobacterium tuberculosis. In response to E. coli LPS, Nlrp12-/- mice showed a slight decrease in IL-1β and increase in IL-6 production, but these levels were not statistically significant. During K. pneumoniae infection, we observed subtle differences in cytokine levels and significantly reduced numbers of monocytes and lymphocytes in Nlrp12-/- mice. However, the physiological relevance of these findings is unclear as no overt differences in the development of lung disease were observed in the Nlrp12-/- mice. Likewise, Nlrp12-/- mice demonstrated pathologies similar to those observed in the wild type mice following M. tuberculosis infection. Together, these data suggest that NLRP12 does not significantly contribute to the in vivo host innate immune response to LPS stimulation, Klebsiella pneumonia infection or Mycobacterium tuberculosis.

Original languageEnglish (US)
Article numbere60842
JournalPLoS One
Volume8
Issue number4
DOIs
StatePublished - Apr 5 2013

Fingerprint

Klebsiella pneumoniae
Mycobacterium tuberculosis
Interleukin-1
immune response
Pulmonary diseases
Lymphocytes
mice
Pathology
Klebsiella Infections
Leucine
Escherichia coli
Interleukin-6
Assays
Nucleotides
interleukin-1
Cytokines
Innate Immunity
infection
Mycobacterium Infections
Aptitude

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Characterization of NLRP12 during the In Vivo Host Immune Response to Klebsiella pneumoniae and Mycobacterium tuberculosis. / Allen, Irving C.; McElvania-TeKippe, Erin; Wilson, Justin E.; Lich, John D.; Arthur, Janelle C.; Sullivan, Jonathan T.; Braunstein, Miriam; Ting, Jenny P Y.

In: PLoS One, Vol. 8, No. 4, e60842, 05.04.2013.

Research output: Contribution to journalArticle

Allen, Irving C. ; McElvania-TeKippe, Erin ; Wilson, Justin E. ; Lich, John D. ; Arthur, Janelle C. ; Sullivan, Jonathan T. ; Braunstein, Miriam ; Ting, Jenny P Y. / Characterization of NLRP12 during the In Vivo Host Immune Response to Klebsiella pneumoniae and Mycobacterium tuberculosis. In: PLoS One. 2013 ; Vol. 8, No. 4.
@article{9a963df4ade149489b0fc783d1922484,
title = "Characterization of NLRP12 during the In Vivo Host Immune Response to Klebsiella pneumoniae and Mycobacterium tuberculosis",
abstract = "The majority of nucleotide binding domain leucine rich repeats-containing (NLR) family members has yet to be functionally characterized. Of the described NLRs, most are considered to be proinflammatory and facilitate IL-1β production. However, a newly defined sub-group of NLRs that function as negative regulators of inflammation have been identified based on their abilities to attenuate NF-κB signaling. NLRP12 (Monarch-1) is a prototypical member of this sub-group that negatively regulates both canonical and noncanonical NF-κB signaling in biochemical assays and in colitis and colon cancer models. The role of NLRP12 in infectious diseases has not been extensively studied. Here, we characterized the innate immune response of Nlrp12-/- mice following airway exposure to LPS, Klebsiella pneumoniae and Mycobacterium tuberculosis. In response to E. coli LPS, Nlrp12-/- mice showed a slight decrease in IL-1β and increase in IL-6 production, but these levels were not statistically significant. During K. pneumoniae infection, we observed subtle differences in cytokine levels and significantly reduced numbers of monocytes and lymphocytes in Nlrp12-/- mice. However, the physiological relevance of these findings is unclear as no overt differences in the development of lung disease were observed in the Nlrp12-/- mice. Likewise, Nlrp12-/- mice demonstrated pathologies similar to those observed in the wild type mice following M. tuberculosis infection. Together, these data suggest that NLRP12 does not significantly contribute to the in vivo host innate immune response to LPS stimulation, Klebsiella pneumonia infection or Mycobacterium tuberculosis.",
author = "Allen, {Irving C.} and Erin McElvania-TeKippe and Wilson, {Justin E.} and Lich, {John D.} and Arthur, {Janelle C.} and Sullivan, {Jonathan T.} and Miriam Braunstein and Ting, {Jenny P Y}",
year = "2013",
month = "4",
day = "5",
doi = "10.1371/journal.pone.0060842",
language = "English (US)",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "4",

}

TY - JOUR

T1 - Characterization of NLRP12 during the In Vivo Host Immune Response to Klebsiella pneumoniae and Mycobacterium tuberculosis

AU - Allen, Irving C.

AU - McElvania-TeKippe, Erin

AU - Wilson, Justin E.

AU - Lich, John D.

AU - Arthur, Janelle C.

AU - Sullivan, Jonathan T.

AU - Braunstein, Miriam

AU - Ting, Jenny P Y

PY - 2013/4/5

Y1 - 2013/4/5

N2 - The majority of nucleotide binding domain leucine rich repeats-containing (NLR) family members has yet to be functionally characterized. Of the described NLRs, most are considered to be proinflammatory and facilitate IL-1β production. However, a newly defined sub-group of NLRs that function as negative regulators of inflammation have been identified based on their abilities to attenuate NF-κB signaling. NLRP12 (Monarch-1) is a prototypical member of this sub-group that negatively regulates both canonical and noncanonical NF-κB signaling in biochemical assays and in colitis and colon cancer models. The role of NLRP12 in infectious diseases has not been extensively studied. Here, we characterized the innate immune response of Nlrp12-/- mice following airway exposure to LPS, Klebsiella pneumoniae and Mycobacterium tuberculosis. In response to E. coli LPS, Nlrp12-/- mice showed a slight decrease in IL-1β and increase in IL-6 production, but these levels were not statistically significant. During K. pneumoniae infection, we observed subtle differences in cytokine levels and significantly reduced numbers of monocytes and lymphocytes in Nlrp12-/- mice. However, the physiological relevance of these findings is unclear as no overt differences in the development of lung disease were observed in the Nlrp12-/- mice. Likewise, Nlrp12-/- mice demonstrated pathologies similar to those observed in the wild type mice following M. tuberculosis infection. Together, these data suggest that NLRP12 does not significantly contribute to the in vivo host innate immune response to LPS stimulation, Klebsiella pneumonia infection or Mycobacterium tuberculosis.

AB - The majority of nucleotide binding domain leucine rich repeats-containing (NLR) family members has yet to be functionally characterized. Of the described NLRs, most are considered to be proinflammatory and facilitate IL-1β production. However, a newly defined sub-group of NLRs that function as negative regulators of inflammation have been identified based on their abilities to attenuate NF-κB signaling. NLRP12 (Monarch-1) is a prototypical member of this sub-group that negatively regulates both canonical and noncanonical NF-κB signaling in biochemical assays and in colitis and colon cancer models. The role of NLRP12 in infectious diseases has not been extensively studied. Here, we characterized the innate immune response of Nlrp12-/- mice following airway exposure to LPS, Klebsiella pneumoniae and Mycobacterium tuberculosis. In response to E. coli LPS, Nlrp12-/- mice showed a slight decrease in IL-1β and increase in IL-6 production, but these levels were not statistically significant. During K. pneumoniae infection, we observed subtle differences in cytokine levels and significantly reduced numbers of monocytes and lymphocytes in Nlrp12-/- mice. However, the physiological relevance of these findings is unclear as no overt differences in the development of lung disease were observed in the Nlrp12-/- mice. Likewise, Nlrp12-/- mice demonstrated pathologies similar to those observed in the wild type mice following M. tuberculosis infection. Together, these data suggest that NLRP12 does not significantly contribute to the in vivo host innate immune response to LPS stimulation, Klebsiella pneumonia infection or Mycobacterium tuberculosis.

UR - http://www.scopus.com/inward/record.url?scp=84875935843&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875935843&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0060842

DO - 10.1371/journal.pone.0060842

M3 - Article

C2 - 23577168

AN - SCOPUS:84875935843

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 4

M1 - e60842

ER -