A narrow repertoire of transcriptional modules responsive to pyogenic bacteria is impaired in patients carrying loss-of-function mutations in MYD88 or IRAK4

Laia Alsina, Elisabeth Israelsson, Matthew C. Altman, Kristen K. Dang, Pegah Ghandil, Laura Israel, Horst Von Bernuth, Nicole Baldwin, Huanying Qin, Zongbo Jin, Romain Banchereau, Esperanza Anguiano, Alexei Ionan, Laurent Abel, Anne Puel, Capucine Picard, Virginia Pascual, Jean Laurent Casanova, Damien J. Chaussabel

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Loss of function of the kinase IRAK4 or the adaptor MyD88 in humans interrupts a pathway critical for pathogen sensing and ignition of inflammation. However, patients with loss-of-function mutations in the genes encoding these factors are, unexpectedly, susceptible to only a limited range of pathogens. We employed a systems approach to investigate transcriptome responses following in vitro exposure of patients' blood to agonists of Toll-like receptors (TLRs) and receptors for interleukin 1 (IL-1Rs) and to whole pathogens. Responses to purified agonists were globally abolished, but variable residual responses were present following exposure to whole pathogens. Further delineation of the latter responses identified a narrow repertoire of transcriptional programs affected by loss of MyD88 function or IRAK4 function. Our work introduces the use of a systems approach for the global assessment of innate immune responses and the characterization of human primary immunodeficiencies.

Original languageEnglish
Pages (from-to)1134-1142
Number of pages9
JournalNature Immunology
Volume15
Issue number12
DOIs
Publication statusPublished - 18 Nov 2014
Externally publishedYes

Fingerprint

Systems Analysis
Bacteria
Mutation
Critical Pathways
Interleukin-1 Receptors
Toll-Like Receptors
Transcriptome
Innate Immunity
Phosphotransferases
Inflammation
Genes
In Vitro Techniques

ASJC Scopus subject areas

  • Immunology

Cite this

A narrow repertoire of transcriptional modules responsive to pyogenic bacteria is impaired in patients carrying loss-of-function mutations in MYD88 or IRAK4. / Alsina, Laia; Israelsson, Elisabeth; Altman, Matthew C.; Dang, Kristen K.; Ghandil, Pegah; Israel, Laura; Von Bernuth, Horst; Baldwin, Nicole; Qin, Huanying; Jin, Zongbo; Banchereau, Romain; Anguiano, Esperanza; Ionan, Alexei; Abel, Laurent; Puel, Anne; Picard, Capucine; Pascual, Virginia; Casanova, Jean Laurent; Chaussabel, Damien J.

In: Nature Immunology, Vol. 15, No. 12, 18.11.2014, p. 1134-1142.

Research output: Contribution to journalArticle

Alsina, L, Israelsson, E, Altman, MC, Dang, KK, Ghandil, P, Israel, L, Von Bernuth, H, Baldwin, N, Qin, H, Jin, Z, Banchereau, R, Anguiano, E, Ionan, A, Abel, L, Puel, A, Picard, C, Pascual, V, Casanova, JL & Chaussabel, DJ 2014, 'A narrow repertoire of transcriptional modules responsive to pyogenic bacteria is impaired in patients carrying loss-of-function mutations in MYD88 or IRAK4', Nature Immunology, vol. 15, no. 12, pp. 1134-1142. https://doi.org/10.1038/ni.3028
Alsina, Laia ; Israelsson, Elisabeth ; Altman, Matthew C. ; Dang, Kristen K. ; Ghandil, Pegah ; Israel, Laura ; Von Bernuth, Horst ; Baldwin, Nicole ; Qin, Huanying ; Jin, Zongbo ; Banchereau, Romain ; Anguiano, Esperanza ; Ionan, Alexei ; Abel, Laurent ; Puel, Anne ; Picard, Capucine ; Pascual, Virginia ; Casanova, Jean Laurent ; Chaussabel, Damien J. / A narrow repertoire of transcriptional modules responsive to pyogenic bacteria is impaired in patients carrying loss-of-function mutations in MYD88 or IRAK4. In: Nature Immunology. 2014 ; Vol. 15, No. 12. pp. 1134-1142.
@article{f09c965b371c4761b1d2ef51faffad3d,
title = "A narrow repertoire of transcriptional modules responsive to pyogenic bacteria is impaired in patients carrying loss-of-function mutations in MYD88 or IRAK4",
abstract = "Loss of function of the kinase IRAK4 or the adaptor MyD88 in humans interrupts a pathway critical for pathogen sensing and ignition of inflammation. However, patients with loss-of-function mutations in the genes encoding these factors are, unexpectedly, susceptible to only a limited range of pathogens. We employed a systems approach to investigate transcriptome responses following in vitro exposure of patients' blood to agonists of Toll-like receptors (TLRs) and receptors for interleukin 1 (IL-1Rs) and to whole pathogens. Responses to purified agonists were globally abolished, but variable residual responses were present following exposure to whole pathogens. Further delineation of the latter responses identified a narrow repertoire of transcriptional programs affected by loss of MyD88 function or IRAK4 function. Our work introduces the use of a systems approach for the global assessment of innate immune responses and the characterization of human primary immunodeficiencies.",
author = "Laia Alsina and Elisabeth Israelsson and Altman, {Matthew C.} and Dang, {Kristen K.} and Pegah Ghandil and Laura Israel and {Von Bernuth}, Horst and Nicole Baldwin and Huanying Qin and Zongbo Jin and Romain Banchereau and Esperanza Anguiano and Alexei Ionan and Laurent Abel and Anne Puel and Capucine Picard and Virginia Pascual and Casanova, {Jean Laurent} and Chaussabel, {Damien J.}",
year = "2014",
month = "11",
day = "18",
doi = "10.1038/ni.3028",
language = "English",
volume = "15",
pages = "1134--1142",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - A narrow repertoire of transcriptional modules responsive to pyogenic bacteria is impaired in patients carrying loss-of-function mutations in MYD88 or IRAK4

AU - Alsina, Laia

AU - Israelsson, Elisabeth

AU - Altman, Matthew C.

AU - Dang, Kristen K.

AU - Ghandil, Pegah

AU - Israel, Laura

AU - Von Bernuth, Horst

AU - Baldwin, Nicole

AU - Qin, Huanying

AU - Jin, Zongbo

AU - Banchereau, Romain

AU - Anguiano, Esperanza

AU - Ionan, Alexei

AU - Abel, Laurent

AU - Puel, Anne

AU - Picard, Capucine

AU - Pascual, Virginia

AU - Casanova, Jean Laurent

AU - Chaussabel, Damien J.

PY - 2014/11/18

Y1 - 2014/11/18

N2 - Loss of function of the kinase IRAK4 or the adaptor MyD88 in humans interrupts a pathway critical for pathogen sensing and ignition of inflammation. However, patients with loss-of-function mutations in the genes encoding these factors are, unexpectedly, susceptible to only a limited range of pathogens. We employed a systems approach to investigate transcriptome responses following in vitro exposure of patients' blood to agonists of Toll-like receptors (TLRs) and receptors for interleukin 1 (IL-1Rs) and to whole pathogens. Responses to purified agonists were globally abolished, but variable residual responses were present following exposure to whole pathogens. Further delineation of the latter responses identified a narrow repertoire of transcriptional programs affected by loss of MyD88 function or IRAK4 function. Our work introduces the use of a systems approach for the global assessment of innate immune responses and the characterization of human primary immunodeficiencies.

AB - Loss of function of the kinase IRAK4 or the adaptor MyD88 in humans interrupts a pathway critical for pathogen sensing and ignition of inflammation. However, patients with loss-of-function mutations in the genes encoding these factors are, unexpectedly, susceptible to only a limited range of pathogens. We employed a systems approach to investigate transcriptome responses following in vitro exposure of patients' blood to agonists of Toll-like receptors (TLRs) and receptors for interleukin 1 (IL-1Rs) and to whole pathogens. Responses to purified agonists were globally abolished, but variable residual responses were present following exposure to whole pathogens. Further delineation of the latter responses identified a narrow repertoire of transcriptional programs affected by loss of MyD88 function or IRAK4 function. Our work introduces the use of a systems approach for the global assessment of innate immune responses and the characterization of human primary immunodeficiencies.

UR - http://www.scopus.com/inward/record.url?scp=84911189024&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84911189024&partnerID=8YFLogxK

U2 - 10.1038/ni.3028

DO - 10.1038/ni.3028

M3 - Article

VL - 15

SP - 1134

EP - 1142

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

IS - 12

ER -