Myc-induced nuclear antigen constrains a latent intestinal epithelial cell-intrinsic anthelmintic pathway

PloS One
Meenu R PillaiMark Bix

Abstract

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.

References

Apr 1, 1966·Australian Veterinary Journal·A W BanksA Korthals
Feb 1, 1984·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·D Dinsdale
Oct 6, 1997·Proceedings of the National Academy of Sciences of the United States of America·N Noben-TrauthW E Paul
Nov 13, 2001·Tropical Medicine & International Health : TM & IH·S Geerts, B Gryseels
Dec 17, 2002·The Journal of Biological Chemistry·Yoshinori ShirafujiAndre J Ouellette
Dec 3, 2003·Trends in Parasitology·Nilanthi R de SilvaLorenzo Savioli
Aug 7, 2004·The Journal of Biological Chemistry·Atsuo MaemotoAndre J Ouellette
Sep 2, 2004·Proceedings of the National Academy of Sciences of the United States of America·David ArtisGary D Wu
Apr 12, 2005·European Journal of Cell Biology·Jens EilbrachtMarion S Schmidt-Zachmann
May 24, 2005·Nature Immunology·Michael E Selsted, Andre J Ouellette
Nov 2, 2005·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Leonard J GiblinChristopher J Frederickson
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 30, 2009·Nature Immunology·Mariko OkamotoMark Bix
Aug 19, 2009·The Journal of Biological Chemistry·Jennifer R Mastroianni, André J Ouellette
Aug 21, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Matthew R Hepworth, Richard K Grencis
Oct 27, 2009·Nature Immunology·Nita H SalzmanNicolaas A Bos
Sep 30, 2010·The Journal of Experimental Medicine·John R GraingerRick M Maizels
Nov 26, 2010·Journal of Innate Immunity·Koji MasudaTokiyoshi Ayabe
May 12, 2011·Cellular and Molecular Life Sciences : CMLS·André Joseph Ouellette
Oct 12, 2012·Seminars in Immunopathology·Joanna E KlementowiczRichard K Grencis
Oct 30, 2012·Nature Chemical Biology·Wei GeChristopher J Schofield
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Jun 12, 2013·Cell Structure and Function·Tetsuya MoriMakoto Tsuneoka
Jul 12, 2013·ACS Chemical Biology·Yunfei ZhangElizabeth M Nolan
Dec 1, 2011·International Journal for Parasitology. Drugs and Drug Resistance·Jozef VercruysseBruno Levecke
May 13, 2014·Nature·Rasheduzzaman ChowdhuryChristopher J Schofield
Jun 20, 2014·Immunological Reviews·Richard K GrencisAllison J Bancroft
Dec 18, 2014·International Journal for Parasitology. Drugs and Drug Resistance·Jacqueline B Matthews
Oct 9, 2015·International Journal for Parasitology. Drugs and Drug Resistance·Thomas GeurdenMatthew J Denwood
Dec 18, 2015·Nature·Jakob von MoltkeRichard M Locksley

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Methods Mentioned

BETA
dissection
ELISA
FACS
IECs
RNAseq
IEC
PMA
ELISAs
scraping
PCR

Software Mentioned

GraphPad Prism
STAR
BWA
Flowjo
GraphPad
Partek Genomics Suite
STATA MP /

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