PMID- 30697697
OWN - NLM
STAT- MEDLINE
DCOM- 20200403
LR  - 20200601
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Print)
IS  - 0009-9104 (Linking)
VI  - 196
IP  - 3
DP  - 2019 Jun
TI  - Low frequency, weak MCP-1 secretion and exhausted immune status of peripheral 
      monocytes were associated with progression of severe enterovirus A71-infected 
      hand, foot and mouth disease.
PG  - 353-363
LID - 10.1111/cei.13267 [doi]
AB  - A minority of hand, foot and mouth disease (HFMD) caused by enterovirus A71 
      (EV-A71) results in severe neural complications. However, whether 
      monocyte-mediated immunity is involved in the disease progression of HFMD remains 
      unknown. One hundred and twenty mild and 103 severe HFMD patients were recruited 
      and enzyme-linked immunosorbent assay (ELISA), flow cytometry and Transwell 
      culture were performed in the study. Peripheral monocyte counts were lower in 
      both absolute counts and frequencies in severe cases compared to mild cases. 
      After screening 10 monocyte-related cytokines by ELISA, only monocyte 
      chemoattractant protein-1 (MCP-1) was found at higher levels in sera of mild 
      cases compared to those with severe symptoms. Monocytes purified from mild cases 
      produced more MCP-1 than the cells from severe patients when stimulated in vitro. 
      We observed that immune exhaustion markers programmed death 1 (PD-1) and 
      programmed death ligand 1 (PD-L1) were highly regulated on the surface of 
      monocytes from severe cases compared to mild cases. PD-L1 blockade induced a 
      higher production of MCP-1 in the supernatant of a Transwell system. The 
      production of MCP-1 also increased following PD-L1 blockade of purified monocytes 
      activated by granulocyte-macrophage colony-stimulating factor (GM-CSF) combined 
      with R848 or EV-A71 virus. Our results indicate that absolute count, frequency 
      and levels of MCP-1 secretion of peripheral monocytes, together with their immune 
      status, probably contribute to differential disease prognosis in 
      EV-A71-associated HFMD.
CI  - (c) 2019 British Society for Immunology.
FAU - Pei, X
AU  - Pei X
AD  - Department of Microbiology and Infectious Disease Center, School of Basic Medical 
      Sciences, Peking University Health Science Center, Beijing, China.
FAU - Fan, X
AU  - Fan X
AD  - Department of Microbiology and Infectious Disease Center, School of Basic Medical 
      Sciences, Peking University Health Science Center, Beijing, China.
AD  - Center of Laboratory Medicine, Beijing Children Hospital, Beijing, China.
FAU - Zhang, H
AU  - Zhang H
AD  - Department of Microbiology and Infectious Disease Center, School of Basic Medical 
      Sciences, Peking University Health Science Center, Beijing, China.
FAU - Duan, H
AU  - Duan H
AD  - Department of Microbiology and Infectious Disease Center, School of Basic Medical 
      Sciences, Peking University Health Science Center, Beijing, China.
FAU - Xu, C
AU  - Xu C
AD  - Department of Microbiology and Infectious Disease Center, School of Basic Medical 
      Sciences, Peking University Health Science Center, Beijing, China.
FAU - Xie, B
AU  - Xie B
AD  - Department of Microbiology and Infectious Disease Center, School of Basic Medical 
      Sciences, Peking University Health Science Center, Beijing, China.
FAU - Wang, L
AU  - Wang L
AD  - National Clinical Key Department of Infectious Disease, Beijing Ditan Hospital, 
      Capital Medical University, Beijing, China.
FAU - Li, X
AU  - Li X
AD  - National Clinical Key Department of Infectious Disease, Beijing Ditan Hospital, 
      Capital Medical University, Beijing, China.
FAU - Peng, Y
AU  - Peng Y
AD  - Department of Microbiology and Infectious Disease Center, School of Basic Medical 
      Sciences, Peking University Health Science Center, Beijing, China.
FAU - Shen, T
AU  - Shen T
AUID- ORCID: 0000-0002-1365-9862
AD  - Department of Microbiology and Infectious Disease Center, School of Basic Medical 
      Sciences, Peking University Health Science Center, Beijing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190217
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Antibodies, Blocking)
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Biomarkers)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (PDCD1 protein, human)
RN  - 0 (Programmed Cell Death 1 Receptor)
SB  - IM
MH  - Antibodies, Blocking/metabolism
MH  - B7-H1 Antigen/metabolism
MH  - Biomarkers/*blood
MH  - Cells, Cultured
MH  - Cellular Senescence
MH  - Chemokine CCL2/*blood
MH  - Child
MH  - Child, Preschool
MH  - Cohort Studies
MH  - Disease Progression
MH  - Enterovirus A, Human/*physiology
MH  - Female
MH  - Hand, Foot and Mouth Disease/diagnosis/*immunology
MH  - Humans
MH  - Immunity, Cellular
MH  - Infant
MH  - Leukocyte Count
MH  - Male
MH  - Monocytes/*immunology
MH  - Programmed Cell Death 1 Receptor/metabolism
MH  - Severity of Illness Index
MH  - Signal Transduction
PMC - PMC6514369
OTO - NOTNLM
OT  - enterovirus A71 (EV-A71)
OT  - foot and mouth disease (HFMD)
OT  - hand
OT  - monocyte
OT  - monocyte chemoattractant protein-1 (MCP-1)
OT  - programmed cell death-1 (PD-1)
COIS- All authors declare no conflicts of interest.
EDAT- 2019/01/31 06:00
MHDA- 2020/04/04 06:00
PMCR- 2020/06/01
CRDT- 2019/01/31 06:00
PHST- 2019/01/14 00:00 [accepted]
PHST- 2019/01/31 06:00 [pubmed]
PHST- 2020/04/04 06:00 [medline]
PHST- 2019/01/31 06:00 [entrez]
PHST- 2020/06/01 00:00 [pmc-release]
AID - CEI13267 [pii]
AID - 10.1111/cei.13267 [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2019 Jun;196(3):353-363. doi: 10.1111/cei.13267. Epub 2019 Feb 
      17.