Innate lymphoid cells have decreased HLA-DR expression but retain their responsiveness to TLR ligands during sepsis

David Cruz-Zárate, Graciela Libier Cabrera-Rivera, Bibiana Patricia Ruiz-Sánchez, Jeanet Serafín-López, Rommel Chacón-Salinas, Constantino López-Macías, Armando Isibasi, Humberto Gallegos-Pérez, Marco Antonio León-Gutiérrez, Eduardo Ferat-Osorio, Lourdes Arriaga-Pizano, Iris Estrada-García, Isabel Wong-Baeza

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Copyright © 2018 by The American Association of Immunologists, Inc. Sepsis, one of the leading causes of death in intensive care units, is caused by a dysregulated host response to infection that leads to life-threatening organ dysfunction. The proinflammatory and anti-inflammatory responses activated by the infecting microorganism become systemic, and the sustained anti-inflammatory response induces a state of immunosuppression that is characterized by decreased expression of HLA-DR on monocytes, T cell apoptosis, and reduced production of TNF-a by monocytes and macrophages in response to TLR ligands. Innate lymphoid cells (ILCs) are lymphocytes that lack Ag-specific receptors and lineage-specific markers; they express HLA-DR and are activated by cytokines and by direct recognition of microbial molecules. In this study, we evaluated if ILCs are affected by the anti-inflammatory response during sepsis. We found that the number of peripheral blood ILCs was decreased in septic patients compared with healthy volunteers; this decrease was caused by a reduction in ILC1 and ILC3 and is associated with apoptosis, because ILCs from septic patients expressed active caspase 3. ILCs from septic patients had decreased HLA-DR expression but increased expression of the activating receptors NKp46 and NKp44; they also showed a sustained expression of CD127 (IL-7R a-chain) and retained their capacity to produce TNF-a in response to TLR ligands. These results indicate that during sepsis, ILCs have decreased HLA-DR expression and die via apoptosis, similar to monocytes and T cells, respectively. However, other effector functions of ILCs (activation through NKp46 and NKp44, TNF-a production) may remain unaffected by the immunosuppressive environment prevailing in septic patients.
Original languageAmerican English
Pages (from-to)3401-3410
Number of pages3059
JournalJournal of Immunology
DOIs
StatePublished - 1 Dec 2018

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HLA-DR Antigens
Sepsis
Lymphocytes
Ligands
Monocytes
Anti-Inflammatory Agents
Apoptosis
Natural Cytotoxicity Triggering Receptor 2
Natural Cytotoxicity Triggering Receptor 1
T-Lymphocytes
Immunosuppressive Agents
Caspase 3
Immunosuppression
Intensive Care Units
Cause of Death
Healthy Volunteers
Macrophages
Cytokines
Infection

Cite this

Cruz-Zárate, David ; Cabrera-Rivera, Graciela Libier ; Ruiz-Sánchez, Bibiana Patricia ; Serafín-López, Jeanet ; Chacón-Salinas, Rommel ; López-Macías, Constantino ; Isibasi, Armando ; Gallegos-Pérez, Humberto ; León-Gutiérrez, Marco Antonio ; Ferat-Osorio, Eduardo ; Arriaga-Pizano, Lourdes ; Estrada-García, Iris ; Wong-Baeza, Isabel. / Innate lymphoid cells have decreased HLA-DR expression but retain their responsiveness to TLR ligands during sepsis. In: Journal of Immunology. 2018 ; pp. 3401-3410.
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abstract = "Copyright {\circledC} 2018 by The American Association of Immunologists, Inc. Sepsis, one of the leading causes of death in intensive care units, is caused by a dysregulated host response to infection that leads to life-threatening organ dysfunction. The proinflammatory and anti-inflammatory responses activated by the infecting microorganism become systemic, and the sustained anti-inflammatory response induces a state of immunosuppression that is characterized by decreased expression of HLA-DR on monocytes, T cell apoptosis, and reduced production of TNF-a by monocytes and macrophages in response to TLR ligands. Innate lymphoid cells (ILCs) are lymphocytes that lack Ag-specific receptors and lineage-specific markers; they express HLA-DR and are activated by cytokines and by direct recognition of microbial molecules. In this study, we evaluated if ILCs are affected by the anti-inflammatory response during sepsis. We found that the number of peripheral blood ILCs was decreased in septic patients compared with healthy volunteers; this decrease was caused by a reduction in ILC1 and ILC3 and is associated with apoptosis, because ILCs from septic patients expressed active caspase 3. ILCs from septic patients had decreased HLA-DR expression but increased expression of the activating receptors NKp46 and NKp44; they also showed a sustained expression of CD127 (IL-7R a-chain) and retained their capacity to produce TNF-a in response to TLR ligands. These results indicate that during sepsis, ILCs have decreased HLA-DR expression and die via apoptosis, similar to monocytes and T cells, respectively. However, other effector functions of ILCs (activation through NKp46 and NKp44, TNF-a production) may remain unaffected by the immunosuppressive environment prevailing in septic patients.",
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Cruz-Zárate, D, Cabrera-Rivera, GL, Ruiz-Sánchez, BP, Serafín-López, J, Chacón-Salinas, R, López-Macías, C, Isibasi, A, Gallegos-Pérez, H, León-Gutiérrez, MA, Ferat-Osorio, E, Arriaga-Pizano, L, Estrada-García, I & Wong-Baeza, I 2018, 'Innate lymphoid cells have decreased HLA-DR expression but retain their responsiveness to TLR ligands during sepsis', Journal of Immunology, pp. 3401-3410. https://doi.org/10.4049/jimmunol.1800735

Innate lymphoid cells have decreased HLA-DR expression but retain their responsiveness to TLR ligands during sepsis. / Cruz-Zárate, David; Cabrera-Rivera, Graciela Libier; Ruiz-Sánchez, Bibiana Patricia; Serafín-López, Jeanet; Chacón-Salinas, Rommel; López-Macías, Constantino; Isibasi, Armando; Gallegos-Pérez, Humberto; León-Gutiérrez, Marco Antonio; Ferat-Osorio, Eduardo; Arriaga-Pizano, Lourdes; Estrada-García, Iris; Wong-Baeza, Isabel.

In: Journal of Immunology, 01.12.2018, p. 3401-3410.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Innate lymphoid cells have decreased HLA-DR expression but retain their responsiveness to TLR ligands during sepsis

AU - Cruz-Zárate, David

AU - Cabrera-Rivera, Graciela Libier

AU - Ruiz-Sánchez, Bibiana Patricia

AU - Serafín-López, Jeanet

AU - Chacón-Salinas, Rommel

AU - López-Macías, Constantino

AU - Isibasi, Armando

AU - Gallegos-Pérez, Humberto

AU - León-Gutiérrez, Marco Antonio

AU - Ferat-Osorio, Eduardo

AU - Arriaga-Pizano, Lourdes

AU - Estrada-García, Iris

AU - Wong-Baeza, Isabel

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Copyright © 2018 by The American Association of Immunologists, Inc. Sepsis, one of the leading causes of death in intensive care units, is caused by a dysregulated host response to infection that leads to life-threatening organ dysfunction. The proinflammatory and anti-inflammatory responses activated by the infecting microorganism become systemic, and the sustained anti-inflammatory response induces a state of immunosuppression that is characterized by decreased expression of HLA-DR on monocytes, T cell apoptosis, and reduced production of TNF-a by monocytes and macrophages in response to TLR ligands. Innate lymphoid cells (ILCs) are lymphocytes that lack Ag-specific receptors and lineage-specific markers; they express HLA-DR and are activated by cytokines and by direct recognition of microbial molecules. In this study, we evaluated if ILCs are affected by the anti-inflammatory response during sepsis. We found that the number of peripheral blood ILCs was decreased in septic patients compared with healthy volunteers; this decrease was caused by a reduction in ILC1 and ILC3 and is associated with apoptosis, because ILCs from septic patients expressed active caspase 3. ILCs from septic patients had decreased HLA-DR expression but increased expression of the activating receptors NKp46 and NKp44; they also showed a sustained expression of CD127 (IL-7R a-chain) and retained their capacity to produce TNF-a in response to TLR ligands. These results indicate that during sepsis, ILCs have decreased HLA-DR expression and die via apoptosis, similar to monocytes and T cells, respectively. However, other effector functions of ILCs (activation through NKp46 and NKp44, TNF-a production) may remain unaffected by the immunosuppressive environment prevailing in septic patients.

AB - Copyright © 2018 by The American Association of Immunologists, Inc. Sepsis, one of the leading causes of death in intensive care units, is caused by a dysregulated host response to infection that leads to life-threatening organ dysfunction. The proinflammatory and anti-inflammatory responses activated by the infecting microorganism become systemic, and the sustained anti-inflammatory response induces a state of immunosuppression that is characterized by decreased expression of HLA-DR on monocytes, T cell apoptosis, and reduced production of TNF-a by monocytes and macrophages in response to TLR ligands. Innate lymphoid cells (ILCs) are lymphocytes that lack Ag-specific receptors and lineage-specific markers; they express HLA-DR and are activated by cytokines and by direct recognition of microbial molecules. In this study, we evaluated if ILCs are affected by the anti-inflammatory response during sepsis. We found that the number of peripheral blood ILCs was decreased in septic patients compared with healthy volunteers; this decrease was caused by a reduction in ILC1 and ILC3 and is associated with apoptosis, because ILCs from septic patients expressed active caspase 3. ILCs from septic patients had decreased HLA-DR expression but increased expression of the activating receptors NKp46 and NKp44; they also showed a sustained expression of CD127 (IL-7R a-chain) and retained their capacity to produce TNF-a in response to TLR ligands. These results indicate that during sepsis, ILCs have decreased HLA-DR expression and die via apoptosis, similar to monocytes and T cells, respectively. However, other effector functions of ILCs (activation through NKp46 and NKp44, TNF-a production) may remain unaffected by the immunosuppressive environment prevailing in septic patients.

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