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
N1 - Publisher Copyright:
Copyright © 2018 by The American Association of Immunologists, Inc.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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 - 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.
UR - http://www.scopus.com/inward/record.url?scp=85056709583&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1800735
DO - 10.4049/jimmunol.1800735
M3 - Artículo
C2 - 30373848
SN - 0022-1767
VL - 201
SP - 3401
EP - 3410
JO - Journal of immunology (Baltimore, Md. : 1950)
JF - Journal of immunology (Baltimore, Md. : 1950)
IS - 11
ER -