NAIP proteins are required for cytosolic detection of specific bacterial ligands in vivo

Isabella Rauch, Jeannette L. Tenthorey, Randilea D. Nichols, Khatoun Al Moussawi, James J. Kang, Chulho Kang, Barbara I. Kazmierczak, Russell E. Vance

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

NLRs (nucleotide-binding domain [NBD] leucine-rich repeat [LRR]-containing proteins) exhibit diverse functions in innate and adaptive immunity. NAIPs (NLR family, apoptosis inhibitory proteins) are NLRs that appear to function as cytosolic immunoreceptors for specific bacterial proteins, including flagellin and the inner rod and needle proteins of bacterial type III secretion systems (T3SSs). Despite strong biochemical evidence implicating NAIPs in specific detection of bacterial ligands, genetic evidence has been lacking. Here we report the use of CRI SPR/Cas9 to generate Naip1-/- and Naip2-/- mice, as well as Naip1-6Δ/Δ mice lacking all functional Naip genes. By challenging Naip1-/- or Naip2-/- mice with specific bacterial ligands in vivo, we demonstrate that Naip1 is uniquely required to detect T3SS needle protein and Naip2 is uniquely required to detect T3SS inner rod protein, but neither Naip1 nor Naip2 is required for detection of flagellin. Previously generated Naip5-/- mice retain some residual responsiveness to flagellin in vivo, whereas Naip1-6Δ/Δ mice fail to respond to cytosolic flagellin, consistent with previous biochemical data implicating NAIP6 in flagellin detection. Our results provide genetic evidence that specific NAIP proteins function to detect specific bacterial proteins in vivo.

Original languageEnglish (US)
Pages (from-to)657-665
Number of pages9
JournalJournal of Experimental Medicine
Volume213
Issue number5
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Fingerprint

Flagellin
Apoptosis
Ligands
Proteins
Bacterial Proteins
Needles
Adaptive Immunity
Innate Immunity
Genes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Rauch, I., Tenthorey, J. L., Nichols, R. D., Al Moussawi, K., Kang, J. J., Kang, C., ... Vance, R. E. (2016). NAIP proteins are required for cytosolic detection of specific bacterial ligands in vivo. Journal of Experimental Medicine, 213(5), 657-665. https://doi.org/10.1084/jem.20151809

NAIP proteins are required for cytosolic detection of specific bacterial ligands in vivo. / Rauch, Isabella; Tenthorey, Jeannette L.; Nichols, Randilea D.; Al Moussawi, Khatoun; Kang, James J.; Kang, Chulho; Kazmierczak, Barbara I.; Vance, Russell E.

In: Journal of Experimental Medicine, Vol. 213, No. 5, 01.01.2016, p. 657-665.

Research output: Contribution to journalArticle

Rauch, I, Tenthorey, JL, Nichols, RD, Al Moussawi, K, Kang, JJ, Kang, C, Kazmierczak, BI & Vance, RE 2016, 'NAIP proteins are required for cytosolic detection of specific bacterial ligands in vivo', Journal of Experimental Medicine, vol. 213, no. 5, pp. 657-665. https://doi.org/10.1084/jem.20151809
Rauch, Isabella ; Tenthorey, Jeannette L. ; Nichols, Randilea D. ; Al Moussawi, Khatoun ; Kang, James J. ; Kang, Chulho ; Kazmierczak, Barbara I. ; Vance, Russell E. / NAIP proteins are required for cytosolic detection of specific bacterial ligands in vivo. In: Journal of Experimental Medicine. 2016 ; Vol. 213, No. 5. pp. 657-665.
@article{b6bba972b5aa4f79a7d5399d1ab2182a,
title = "NAIP proteins are required for cytosolic detection of specific bacterial ligands in vivo",
abstract = "NLRs (nucleotide-binding domain [NBD] leucine-rich repeat [LRR]-containing proteins) exhibit diverse functions in innate and adaptive immunity. NAIPs (NLR family, apoptosis inhibitory proteins) are NLRs that appear to function as cytosolic immunoreceptors for specific bacterial proteins, including flagellin and the inner rod and needle proteins of bacterial type III secretion systems (T3SSs). Despite strong biochemical evidence implicating NAIPs in specific detection of bacterial ligands, genetic evidence has been lacking. Here we report the use of CRI SPR/Cas9 to generate Naip1-/- and Naip2-/- mice, as well as Naip1-6Δ/Δ mice lacking all functional Naip genes. By challenging Naip1-/- or Naip2-/- mice with specific bacterial ligands in vivo, we demonstrate that Naip1 is uniquely required to detect T3SS needle protein and Naip2 is uniquely required to detect T3SS inner rod protein, but neither Naip1 nor Naip2 is required for detection of flagellin. Previously generated Naip5-/- mice retain some residual responsiveness to flagellin in vivo, whereas Naip1-6Δ/Δ mice fail to respond to cytosolic flagellin, consistent with previous biochemical data implicating NAIP6 in flagellin detection. Our results provide genetic evidence that specific NAIP proteins function to detect specific bacterial proteins in vivo.",
author = "Isabella Rauch and Tenthorey, {Jeannette L.} and Nichols, {Randilea D.} and {Al Moussawi}, Khatoun and Kang, {James J.} and Chulho Kang and Kazmierczak, {Barbara I.} and Vance, {Russell E.}",
year = "2016",
month = "1",
day = "1",
doi = "10.1084/jem.20151809",
language = "English (US)",
volume = "213",
pages = "657--665",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "5",

}

TY - JOUR

T1 - NAIP proteins are required for cytosolic detection of specific bacterial ligands in vivo

AU - Rauch, Isabella

AU - Tenthorey, Jeannette L.

AU - Nichols, Randilea D.

AU - Al Moussawi, Khatoun

AU - Kang, James J.

AU - Kang, Chulho

AU - Kazmierczak, Barbara I.

AU - Vance, Russell E.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - NLRs (nucleotide-binding domain [NBD] leucine-rich repeat [LRR]-containing proteins) exhibit diverse functions in innate and adaptive immunity. NAIPs (NLR family, apoptosis inhibitory proteins) are NLRs that appear to function as cytosolic immunoreceptors for specific bacterial proteins, including flagellin and the inner rod and needle proteins of bacterial type III secretion systems (T3SSs). Despite strong biochemical evidence implicating NAIPs in specific detection of bacterial ligands, genetic evidence has been lacking. Here we report the use of CRI SPR/Cas9 to generate Naip1-/- and Naip2-/- mice, as well as Naip1-6Δ/Δ mice lacking all functional Naip genes. By challenging Naip1-/- or Naip2-/- mice with specific bacterial ligands in vivo, we demonstrate that Naip1 is uniquely required to detect T3SS needle protein and Naip2 is uniquely required to detect T3SS inner rod protein, but neither Naip1 nor Naip2 is required for detection of flagellin. Previously generated Naip5-/- mice retain some residual responsiveness to flagellin in vivo, whereas Naip1-6Δ/Δ mice fail to respond to cytosolic flagellin, consistent with previous biochemical data implicating NAIP6 in flagellin detection. Our results provide genetic evidence that specific NAIP proteins function to detect specific bacterial proteins in vivo.

AB - NLRs (nucleotide-binding domain [NBD] leucine-rich repeat [LRR]-containing proteins) exhibit diverse functions in innate and adaptive immunity. NAIPs (NLR family, apoptosis inhibitory proteins) are NLRs that appear to function as cytosolic immunoreceptors for specific bacterial proteins, including flagellin and the inner rod and needle proteins of bacterial type III secretion systems (T3SSs). Despite strong biochemical evidence implicating NAIPs in specific detection of bacterial ligands, genetic evidence has been lacking. Here we report the use of CRI SPR/Cas9 to generate Naip1-/- and Naip2-/- mice, as well as Naip1-6Δ/Δ mice lacking all functional Naip genes. By challenging Naip1-/- or Naip2-/- mice with specific bacterial ligands in vivo, we demonstrate that Naip1 is uniquely required to detect T3SS needle protein and Naip2 is uniquely required to detect T3SS inner rod protein, but neither Naip1 nor Naip2 is required for detection of flagellin. Previously generated Naip5-/- mice retain some residual responsiveness to flagellin in vivo, whereas Naip1-6Δ/Δ mice fail to respond to cytosolic flagellin, consistent with previous biochemical data implicating NAIP6 in flagellin detection. Our results provide genetic evidence that specific NAIP proteins function to detect specific bacterial proteins in vivo.

UR - http://www.scopus.com/inward/record.url?scp=84969257253&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84969257253&partnerID=8YFLogxK

U2 - 10.1084/jem.20151809

DO - 10.1084/jem.20151809

M3 - Article

VL - 213

SP - 657

EP - 665

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 5

ER -