PMID- 36604951
OWN - NLM
STAT- MEDLINE
DCOM- 20230302
LR  - 20230315
IS  - 1440-1711 (Electronic)
IS  - 0818-9641 (Linking)
VI  - 101
IP  - 3
DP  - 2023 Mar
TI  - Longitudinal analysis of mucosa-associated invariant T cells in sepsis reveals 
      their early numerical decline with prognostic implications and a progressive loss 
      of antimicrobial functions.
PG  - 249-261
LID - 10.1111/imcb.12619 [doi]
AB  - Sepsis-elicited immunosuppression elevates the risk of secondary infections. We 
      used a clinically relevant mouse model and serial peripheral blood samples from 
      patients to assess the antimicrobial activities of mucosa-associated invariant T 
      (MAIT) cells in sepsis. Hepatic and splenic MAIT cells from B6-MAIT(CAST) mice 
      displayed increased CD69 expression and a robust interferon-gamma (IFNgamma) production 
      capacity shortly after sublethal cecal ligation and puncture, but not at a late 
      timepoint. Peripheral blood MAIT cell frequencies were reduced in septic patients 
      at the time of intensive care unit (ICU) admission, and more dramatically so 
      among nonsurvivors, suggesting the predictive usefulness of early MAIT cell 
      enumeration. In addition, at ICU admission, MAIT cells from sepsis survivors 
      launched stronger IFNgamma responses to several bacterial species compared with those 
      from patients who subsequently died of sepsis. Of note, while low human leukocyte 
      antigen (HLA)-DR(+) monocyte frequencies, widely regarded as a surrogate 
      indicator of sepsis-induced immunosuppression, were gradually corrected, the 
      numerical insufficiency of MAIT cells was not resolved over time, and their CD69 
      expression continued to decline. MAIT cell responses to bacterial pathogens, a 
      major histocompatibility complex-related protein 1 (MR1) ligand, and interleukin 
      (IL)-12 and IL-18 were also progressively lost during sepsis and did not recover 
      by the time of ICU/hospital discharge. We propose that MAIT cell dysfunctions 
      contribute to post-sepsis immunosuppression.
CI  - (c) 2023 The Authors. Immunology & Cell Biology published by John Wiley & Sons 
      Australia, Ltd on behalf of the Australian and New Zealand Society for 
      Immunology, Inc.
FAU - Choi, Joshua
AU  - Choi J
AD  - Department of Microbiology and Immunology, Western University, London, Ontario, 
      Canada.
FAU - Schmerk, Crystal L
AU  - Schmerk CL
AD  - Department of Microbiology and Immunology, Western University, London, Ontario, 
      Canada.
FAU - Mele, Tina S
AU  - Mele TS
AD  - Division of Critical Care Medicine, Department of Medicine, Western University, 
      London, Ontario, Canada.
AD  - Division of General Surgery, Department of Surgery, Western University, London, 
      Ontario, Canada.
FAU - Rudak, Patrick T
AU  - Rudak PT
AD  - Department of Microbiology and Immunology, Western University, London, Ontario, 
      Canada.
FAU - Wardell, Christine M
AU  - Wardell CM
AD  - Department of Microbiology and Immunology, Western University, London, Ontario, 
      Canada.
FAU - Deng, Gansen
AU  - Deng G
AD  - Department of Statistical and Actuarial Sciences, Western University, London, 
      Ontario, Canada.
FAU - Pavri, Farzan R
AU  - Pavri FR
AD  - Department of Microbiology and Immunology, Western University, London, Ontario, 
      Canada.
FAU - Kim, Kyoungok
AU  - Kim K
AD  - Department of Microbiology and Immunology, Western University, London, Ontario, 
      Canada.
FAU - Cepinskas, Gediminas
AU  - Cepinskas G
AD  - Centre for Critical Illness Research, Lawson Health Research Institute, London, 
      Ontario, Canada.
AD  - Department of Medical Biophysics, Western University, London, Ontario, Canada.
FAU - He, Wenqing
AU  - He W
AD  - Department of Statistical and Actuarial Sciences, Western University, London, 
      Ontario, Canada.
FAU - Haeryfar, Sm Mansour
AU  - Haeryfar SM
AUID- ORCID: 0000-0002-1125-8176
AD  - Department of Microbiology and Immunology, Western University, London, Ontario, 
      Canada.
AD  - Division of General Surgery, Department of Surgery, Western University, London, 
      Ontario, Canada.
AD  - Division of Clinical Immunology and Allergy, Department of Medicine, Western 
      University, London, Ontario, Canada.
LA  - eng
GR  - PJT-156295/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230201
PL  - United States
TA  - Immunol Cell Biol
JT  - Immunology and cell biology
JID - 8706300
RN  - 187348-17-0 (Interleukin-12)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Anti-Infective Agents)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - *Mucosal-Associated Invariant T Cells
MH  - Prognosis
MH  - Interleukin-12/metabolism
MH  - HLA-DR Antigens/metabolism
MH  - *Sepsis/metabolism
MH  - *Anti-Infective Agents/metabolism
OTO - NOTNLM
OT  - MAIT cells
OT  - critical illness
OT  - immunosuppression
OT  - mortality
OT  - opportunistic infections
OT  - sepsis
EDAT- 2023/01/07 06:00
MHDA- 2023/03/03 06:00
CRDT- 2023/01/06 01:34
PHST- 2022/11/24 00:00 [revised]
PHST- 2022/07/13 00:00 [received]
PHST- 2023/01/03 00:00 [accepted]
PHST- 2023/01/07 06:00 [pubmed]
PHST- 2023/03/03 06:00 [medline]
PHST- 2023/01/06 01:34 [entrez]
AID - 10.1111/imcb.12619 [doi]
PST - ppublish
SO  - Immunol Cell Biol. 2023 Mar;101(3):249-261. doi: 10.1111/imcb.12619. Epub 2023 
      Feb 1.