Myc-induced nuclear antigen constrains a latent intestinal epithelial cell-intrinsic anthelmintic pathway.
Animals
Cytokines
/ analysis
Epithelial Cells
/ cytology
Intestines
/ cytology
Mice
Mice, Inbred C57BL
Mice, Knockout
Neoplasm Proteins
/ deficiency
Nuclear Proteins
/ deficiency
Recombinant Proteins
/ biosynthesis
Th1 Cells
/ cytology
Th2 Cells
/ cytology
Transcriptome
Trichuriasis
/ drug therapy
Trichuris
/ drug effects
alpha-Defensins
/ genetics
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
28
03
2018
accepted:
09
01
2019
entrez:
27
2
2019
pubmed:
27
2
2019
medline:
2
11
2019
Statut:
epublish
Résumé
Expulsion of parasitic gastrointestinal nematodes requires diverse effector mechanisms coordinated by a Th2-type response. The evolutionarily conserved JmjC protein; Myc Induced Nuclear Antigen (Mina) has been shown to repress IL4, a key Th2 cytokine, suggesting Mina may negatively regulate nematode expulsion. Here we report that expulsion of the parasitic nematode Trichuris muris was indeed accelerated in Mina deficient mice. Unexpectedly, this was associated not with an elevated Th2- but rather an impaired Th1-type response. Further reciprocal bone marrow chimera and conditional KO experiments demonstrated that retarded parasite expulsion and a normal Th1-type response both required Mina in intestinal epithelial cells (IECs). Transcriptional profiling experiments in IECs revealed anti-microbial α-defensin peptides to be the major target of Mina-dependent retention of worms in infected mice. In vitro exposure to recombinant α-defensin peptides caused cytotoxic damage to whipworms. These results identify a latent IEC-intrinsic anthelmintic pathway actively constrained by Mina and point to α-defensins as important effectors that together with Mina may be attractive therapeutic targets for the control of nematode infection.
Identifiants
pubmed: 30807587
doi: 10.1371/journal.pone.0211244
pii: PONE-D-19-00748
pmc: PMC6391002
doi:
Substances chimiques
Cytokines
0
Mina53 protein, mouse
0
Neoplasm Proteins
0
Nuclear Proteins
0
Recombinant Proteins
0
alpha-Defensins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0211244Subventions
Organisme : Medical Research Council
ID : MR/N021053/1
Pays : United Kingdom
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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