PMID- 36827187
OWN - NLM
STAT- MEDLINE
DCOM- 20230403
LR  - 20240109
IS  - 2211-1247 (Electronic)
VI  - 42
IP  - 3
DP  - 2023 Mar 28
TI  - IL-18BP mediates the balance between protective and pathological immune responses 
      to Toxoplasma gondii.
PG  - 112147
LID - S2211-1247(23)00158-4 [pii]
LID - 10.1016/j.celrep.2023.112147 [doi]
AB  - Interleukin-18 (IL-18) promotes natural killer (NK) and T cell production of 
      interferon (IFN)-gamma, a key factor in resistance to Toxoplasma gondii, but previous 
      work has shown a limited role for endogenous IL-18 in control of this parasite. 
      Although infection with T. gondii results in release of IL-18, the production of 
      IFN-gamma induces high levels of the IL-18 binding protein (IL-18BP). Antagonism of 
      IL-18BP with a "decoy-to-the-decoy" (D2D) IL-18 construct that does not signal 
      but rather binds IL-18BP results in enhanced innate lymphoid cell (ILC) and 
      T cell responses and improved parasite control. In addition, the use of IL-18 
      resistant to IL-18BP ("decoy-resistant" IL-18 [DR-18]) is more effective than 
      exogenous IL-18 at promoting innate resistance to infection. DR-18 enhances 
      CD4(+) T cell production of IFN-gamma but results in CD4(+) T cell-mediated 
      pathology. Thus, endogenous IL-18BP restrains aberrant immune pathology, and this 
      study highlights strategies that can be used to tune this regulatory pathway for 
      optimal anti-pathogen responses.
CI  - Copyright (c) 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Clark, Joseph T
AU  - Clark JT
AD  - Department of Pathobiology, University of Pennsylvania School of Veterinary 
      Medicine, Philadelphia, PA 19104, USA.
FAU - Weizman, Orr-El
AU  - Weizman OE
AD  - Department of Immunobiology, Yale School of Medicine, New Haven, CT 06519, USA.
FAU - Aldridge, Daniel L
AU  - Aldridge DL
AD  - Department of Pathobiology, University of Pennsylvania School of Veterinary 
      Medicine, Philadelphia, PA 19104, USA.
FAU - Shallberg, Lindsey A
AU  - Shallberg LA
AD  - Department of Pathobiology, University of Pennsylvania School of Veterinary 
      Medicine, Philadelphia, PA 19104, USA.
FAU - Eberhard, Julia
AU  - Eberhard J
AD  - Department of Pathobiology, University of Pennsylvania School of Veterinary 
      Medicine, Philadelphia, PA 19104, USA.
FAU - Lanzar, Zachary
AU  - Lanzar Z
AD  - Department of Pathobiology, University of Pennsylvania School of Veterinary 
      Medicine, Philadelphia, PA 19104, USA.
FAU - Wasche, Devon
AU  - Wasche D
AD  - Department of Immunobiology, Yale School of Medicine, New Haven, CT 06519, USA.
FAU - Huck, John D
AU  - Huck JD
AD  - Department of Immunobiology, Yale School of Medicine, New Haven, CT 06519, USA.
FAU - Zhou, Ting
AU  - Zhou T
AD  - Department of Immunobiology, Yale School of Medicine, New Haven, CT 06519, USA.
FAU - Ring, Aaron M
AU  - Ring AM
AD  - Department of Immunobiology, Yale School of Medicine, New Haven, CT 06519, USA. 
      Electronic address: aaron.ring@yale.edu.
FAU - Hunter, Christopher A
AU  - Hunter CA
AD  - Department of Pathobiology, University of Pennsylvania School of Veterinary 
      Medicine, Philadelphia, PA 19104, USA. Electronic address: chunter@vet.upenn.edu.
LA  - eng
GR  - R01 AI125563/AI/NIAID NIH HHS/United States
GR  - T32 AI007532/AI/NIAID NIH HHS/United States
GR  - DP5 OD023088/OD/NIH HHS/United States
GR  - T32 CA193200/CA/NCI NIH HHS/United States
GR  - U01 CA233096/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230223
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Interleukin-18)
RN  - 0 (interleukin-18 binding protein)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Humans
MH  - Animals
MH  - *Toxoplasma
MH  - Interleukin-18/metabolism
MH  - Killer Cells, Natural
MH  - Interleukin-12/metabolism
MH  - Immunity, Innate
MH  - *Toxoplasmosis, Animal
PMC - PMC10131179
MID - NIHMS1887264
OTO - NOTNLM
OT  - CD4 T cells
OT  - CD8 T cell
OT  - CP: Immunology
OT  - CP: Microbiology
OT  - IFN-gamma
OT  - IL-18
OT  - IL-18 binding protein
OT  - NK cell
OT  - Toxoplasma
OT  - cytokine
OT  - infection
OT  - pathology
COIS- Declaration of interests A.M.R. and T.Z. are named inventors on a patent 
      application that describes the DR-18 and D2D molecules. A.M.R. is the founder and 
      a Director of Simcha Therapeutics, the commercial licensee of DR-18.
EDAT- 2023/02/25 06:00
MHDA- 2023/04/03 06:41
PMCR- 2023/04/26
CRDT- 2023/02/24 12:37
PHST- 2022/02/14 00:00 [received]
PHST- 2022/12/02 00:00 [revised]
PHST- 2023/02/07 00:00 [accepted]
PHST- 2023/04/03 06:41 [medline]
PHST- 2023/02/25 06:00 [pubmed]
PHST- 2023/02/24 12:37 [entrez]
PHST- 2023/04/26 00:00 [pmc-release]
AID - S2211-1247(23)00158-4 [pii]
AID - 10.1016/j.celrep.2023.112147 [doi]
PST - ppublish
SO  - Cell Rep. 2023 Mar 28;42(3):112147. doi: 10.1016/j.celrep.2023.112147. Epub 2023 
      Feb 23.