Human Adaptive Immunity Rescues an Inborn Error of Innate Immunity

Laura Israel, Ying Wang, Katarzyna Bulek, Erika Della Mina, Zhao Zhang, Vincent Pedergnana, Maya Chrabieh, Nicole A. Lemmens, Vanessa Sancho-Shimizu, Marc Descatoire, Théo Lasseau, Elisabeth Israelsson, Lazaro Lorenzo, Ling Yun, Aziz Belkadi, Andrew Moran, Leonard E. Weisman, François Vandenesch, Frederic Batteux, Sandra WellerMichael Levin, Jethro Herberg, Avinash Abhyankar, Carolina Prando, Yuval Itan, Willem J.B. van Wamel, Capucine Picard, Laurent Abel, Damien Chaussabel, Xiaoxia Li, Bruce Beutler, Peter D. Arkwright, Jean Laurent Casanova, Anne Puel

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The molecular basis of the incomplete penetrance of monogenic disorders is unclear. We describe here eight related individuals with autosomal recessive TIRAP deficiency. Life-threatening staphylococcal disease occurred during childhood in the proband, but not in the other seven homozygotes. Responses to all Toll-like receptor 1/2 (TLR1/2), TLR2/6, and TLR4 agonists were impaired in the fibroblasts and leukocytes of all TIRAP-deficient individuals. However, the whole-blood response to the TLR2/6 agonist staphylococcal lipoteichoic acid (LTA) was abolished only in the index case individual, the only family member lacking LTA-specific antibodies (Abs). This defective response was reversed in the patient, but not in interleukin-1 receptor-associated kinase 4 (IRAK-4)-deficient individuals, by anti-LTA monoclonal antibody (mAb). Anti-LTA mAb also rescued the macrophage response in mice lacking TIRAP, but not TLR2 or MyD88. Thus, acquired anti-LTA Abs rescue TLR2-dependent immunity to staphylococcal LTA in individuals with inherited TIRAP deficiency, accounting for incomplete penetrance. Combined TIRAP and anti-LTA Ab deficiencies underlie staphylococcal disease in this patient.

Original languageEnglish (US)
Pages (from-to)789-800.e10
JournalCell
Volume168
Issue number5
DOIs
StatePublished - Feb 23 2017

Fingerprint

Adaptive Immunity
Innate Immunity
Penetrance
Toll-Like Receptor 1
Interleukin-1 Receptor-Associated Kinases
Monoclonal Antibodies
Toll-Like Receptor 2
Antibodies
Macrophages
Homozygote
Fibroblasts
lipoteichoic acid
Immunity
Leukocytes
Blood

Keywords

  • anti-LTA antibodies
  • incomplete clinical penetrance
  • lipoteichoic acid
  • LTA
  • primary immunodeficiency
  • staphylococcus aureus
  • TIRAP
  • toll-like receptors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Israel, L., Wang, Y., Bulek, K., Della Mina, E., Zhang, Z., Pedergnana, V., ... Puel, A. (2017). Human Adaptive Immunity Rescues an Inborn Error of Innate Immunity. Cell, 168(5), 789-800.e10. https://doi.org/10.1016/j.cell.2017.01.039

Human Adaptive Immunity Rescues an Inborn Error of Innate Immunity. / Israel, Laura; Wang, Ying; Bulek, Katarzyna; Della Mina, Erika; Zhang, Zhao; Pedergnana, Vincent; Chrabieh, Maya; Lemmens, Nicole A.; Sancho-Shimizu, Vanessa; Descatoire, Marc; Lasseau, Théo; Israelsson, Elisabeth; Lorenzo, Lazaro; Yun, Ling; Belkadi, Aziz; Moran, Andrew; Weisman, Leonard E.; Vandenesch, François; Batteux, Frederic; Weller, Sandra; Levin, Michael; Herberg, Jethro; Abhyankar, Avinash; Prando, Carolina; Itan, Yuval; van Wamel, Willem J.B.; Picard, Capucine; Abel, Laurent; Chaussabel, Damien; Li, Xiaoxia; Beutler, Bruce; Arkwright, Peter D.; Casanova, Jean Laurent; Puel, Anne.

In: Cell, Vol. 168, No. 5, 23.02.2017, p. 789-800.e10.

Research output: Contribution to journalArticle

Israel, L, Wang, Y, Bulek, K, Della Mina, E, Zhang, Z, Pedergnana, V, Chrabieh, M, Lemmens, NA, Sancho-Shimizu, V, Descatoire, M, Lasseau, T, Israelsson, E, Lorenzo, L, Yun, L, Belkadi, A, Moran, A, Weisman, LE, Vandenesch, F, Batteux, F, Weller, S, Levin, M, Herberg, J, Abhyankar, A, Prando, C, Itan, Y, van Wamel, WJB, Picard, C, Abel, L, Chaussabel, D, Li, X, Beutler, B, Arkwright, PD, Casanova, JL & Puel, A 2017, 'Human Adaptive Immunity Rescues an Inborn Error of Innate Immunity', Cell, vol. 168, no. 5, pp. 789-800.e10. https://doi.org/10.1016/j.cell.2017.01.039
Israel L, Wang Y, Bulek K, Della Mina E, Zhang Z, Pedergnana V et al. Human Adaptive Immunity Rescues an Inborn Error of Innate Immunity. Cell. 2017 Feb 23;168(5):789-800.e10. https://doi.org/10.1016/j.cell.2017.01.039
Israel, Laura ; Wang, Ying ; Bulek, Katarzyna ; Della Mina, Erika ; Zhang, Zhao ; Pedergnana, Vincent ; Chrabieh, Maya ; Lemmens, Nicole A. ; Sancho-Shimizu, Vanessa ; Descatoire, Marc ; Lasseau, Théo ; Israelsson, Elisabeth ; Lorenzo, Lazaro ; Yun, Ling ; Belkadi, Aziz ; Moran, Andrew ; Weisman, Leonard E. ; Vandenesch, François ; Batteux, Frederic ; Weller, Sandra ; Levin, Michael ; Herberg, Jethro ; Abhyankar, Avinash ; Prando, Carolina ; Itan, Yuval ; van Wamel, Willem J.B. ; Picard, Capucine ; Abel, Laurent ; Chaussabel, Damien ; Li, Xiaoxia ; Beutler, Bruce ; Arkwright, Peter D. ; Casanova, Jean Laurent ; Puel, Anne. / Human Adaptive Immunity Rescues an Inborn Error of Innate Immunity. In: Cell. 2017 ; Vol. 168, No. 5. pp. 789-800.e10.
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abstract = "The molecular basis of the incomplete penetrance of monogenic disorders is unclear. We describe here eight related individuals with autosomal recessive TIRAP deficiency. Life-threatening staphylococcal disease occurred during childhood in the proband, but not in the other seven homozygotes. Responses to all Toll-like receptor 1/2 (TLR1/2), TLR2/6, and TLR4 agonists were impaired in the fibroblasts and leukocytes of all TIRAP-deficient individuals. However, the whole-blood response to the TLR2/6 agonist staphylococcal lipoteichoic acid (LTA) was abolished only in the index case individual, the only family member lacking LTA-specific antibodies (Abs). This defective response was reversed in the patient, but not in interleukin-1 receptor-associated kinase 4 (IRAK-4)-deficient individuals, by anti-LTA monoclonal antibody (mAb). Anti-LTA mAb also rescued the macrophage response in mice lacking TIRAP, but not TLR2 or MyD88. Thus, acquired anti-LTA Abs rescue TLR2-dependent immunity to staphylococcal LTA in individuals with inherited TIRAP deficiency, accounting for incomplete penetrance. Combined TIRAP and anti-LTA Ab deficiencies underlie staphylococcal disease in this patient.",
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AU - Della Mina, Erika

AU - Zhang, Zhao

AU - Pedergnana, Vincent

AU - Chrabieh, Maya

AU - Lemmens, Nicole A.

AU - Sancho-Shimizu, Vanessa

AU - Descatoire, Marc

AU - Lasseau, Théo

AU - Israelsson, Elisabeth

AU - Lorenzo, Lazaro

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AU - Belkadi, Aziz

AU - Moran, Andrew

AU - Weisman, Leonard E.

AU - Vandenesch, François

AU - Batteux, Frederic

AU - Weller, Sandra

AU - Levin, Michael

AU - Herberg, Jethro

AU - Abhyankar, Avinash

AU - Prando, Carolina

AU - Itan, Yuval

AU - van Wamel, Willem J.B.

AU - Picard, Capucine

AU - Abel, Laurent

AU - Chaussabel, Damien

AU - Li, Xiaoxia

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AU - Arkwright, Peter D.

AU - Casanova, Jean Laurent

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KW - staphylococcus aureus

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