PMID- 34371178
OWN - NLM
STAT- MEDLINE
DCOM- 20220407
LR  - 20230106
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 30
IP  - 1
DP  - 2022 Jan 5
TI  - IL-6-elafin genetically modified macrophages as a lung immunotherapeutic strategy 
      against Pseudomonas aeruginosa infections.
PG  - 355-369
LID - S1525-0016(21)00401-9 [pii]
LID - 10.1016/j.ymthe.2021.08.007 [doi]
AB  - Pseudomonas aeruginosa (P.a) infections are a major public health issue in 
      ventilator-associated pneumoniae, cystic fibrosis, and chronic obstructive 
      pulmonary disease exacerbations. P.a is multidrug resistant, and there is an 
      urgent need to develop new therapeutic approaches. Here, we evaluated the effect 
      of direct pulmonary transplantation of gene-modified (elafin and interleukin 
      [IL]-6) syngeneic macrophages in a mouse model of acute P.a infection. Wild-type 
      (WT) or Elafin-transgenic (eTg) alveolar macrophages (AMs) or bone marrow-derived 
      macrophages (BMDMs) were recovered from bronchoalveolar lavage or generated from 
      WT or eTg mouse bone marrow. Cells were modified with adenovirus IL-6 (Ad-IL-6), 
      characterized in vitro, and transferred by oropharyngeal instillation in the 
      lungs of naive mice. The protective effect was assessed during P.a acute 
      infection (survival studies, mechanistic studies of the inflammatory response). 
      We show that a single bolus of genetically modified syngeneic AMs or BMDMs 
      provided protection in our P.a-induced model. Mechanistically, Elafin-modified 
      AMs had an IL-6-IL-10-IL-4R-IL-22-antimicrobial molecular signature that, in 
      synergy with IL-6, enhanced epithelial cell proliferation and tissue repair in 
      the alveolar unit. We believe that this innovative cell therapy strategy could be 
      of value in acute bacterial infections in the lung.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Kheir, Saade
AU  - Kheir S
AD  - INSERM U1152, Laboratoire d'Excellence Inflamex, Universite de Paris, Hopital 
      Bichat-Claude-Bernard, Paris 75014, France.
FAU - Villeret, Berengere
AU  - Villeret B
AD  - INSERM U1152, Laboratoire d'Excellence Inflamex, Universite de Paris, Hopital 
      Bichat-Claude-Bernard, Paris 75014, France.
FAU - Garcia-Verdugo, Ignacio
AU  - Garcia-Verdugo I
AD  - INSERM U1152, Laboratoire d'Excellence Inflamex, Universite de Paris, Hopital 
      Bichat-Claude-Bernard, Paris 75014, France.
FAU - Sallenave, Jean-Michel
AU  - Sallenave JM
AD  - INSERM U1152, Laboratoire d'Excellence Inflamex, Universite de Paris, Hopital 
      Bichat-Claude-Bernard, Paris 75014, France. Electronic address: 
      jean-michel.sallenave@inserm.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210808
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Elafin)
RN  - 0 (Interleukin-6)
SB  - IM
MH  - Animals
MH  - Elafin
MH  - Immunotherapy
MH  - Interleukin-6/genetics
MH  - Lung/microbiology
MH  - Macrophages
MH  - Macrophages, Alveolar
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Pseudomonas Infections/genetics/microbiology/therapy
MH  - Pseudomonas aeruginosa/genetics
PMC - PMC8753374
OTO - NOTNLM
OT  - IL-6
OT  - Pseudomonas aeruginosa
OT  - adenovirus
OT  - adoptive transfer
OT  - alveolar macrophages
OT  - anti-inflammatory
OT  - elafin
OT  - gene therapy
OT  - infection
OT  - inflammation
OT  - lung
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2021/08/10 06:00
MHDA- 2022/04/08 06:00
PMCR- 2023/01/05
CRDT- 2021/08/09 20:13
PHST- 2021/01/30 00:00 [received]
PHST- 2021/05/28 00:00 [revised]
PHST- 2021/07/29 00:00 [accepted]
PHST- 2021/08/10 06:00 [pubmed]
PHST- 2022/04/08 06:00 [medline]
PHST- 2021/08/09 20:13 [entrez]
PHST- 2023/01/05 00:00 [pmc-release]
AID - S1525-0016(21)00401-9 [pii]
AID - 10.1016/j.ymthe.2021.08.007 [doi]
PST - ppublish
SO  - Mol Ther. 2022 Jan 5;30(1):355-369. doi: 10.1016/j.ymthe.2021.08.007. Epub 2021 
      Aug 8.