PT  - JOURNAL ARTICLE
AU  - Martin Schwarzer
AU  - Petra Hermanova
AU  - Dagmar Srutkova
AU  - Jaroslav Golias
AU  - Tomas Hudcovic
AU  - Marek Sinkora
AU  - Johnnie Akgün
AU  - Christian Zwicker
AU  - Ursula Wiedermann
AU  - Ludmila Tuckova
AU  - Hana Kozakova
AU  - Irma Schabussova
TI  - Germ-free mice exhibit mast cells with impaired functionality and gut homing and do not develop food allergy
AID  - 10.1101/394213
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 394213
4099  - http://biorxiv.org/content/early/2018/08/17/394213.short
4100  - http://biorxiv.org/content/early/2018/08/17/394213.full
AB  - Background Mucosal mast cells (MC) are key players in IgE-mediated food allergy (FA). The evidence on the interaction between gut microbiota, MC and susceptibility to FA is contradictory.Objective We tested the hypothesis that commensal bacteria are essential for MC migration to the gut and their maturation impacting the susceptibility to FA.Methods The development and severity of FA symptoms was studied in sensitized germ-free (GF), conventional (CV) and mice mono-colonized with L. plantarum WCFS1 or co-housed with CV mice. MC were phenotypically and functionally characterized.Results Systemic sensitization and oral challenge of GF mice with ovalbumin led to increased levels of specific IgE in serum compared to CV mice. Remarkably, despite the high levels of sensitization, GF mice did not develop diarrhea or anaphylactic hypothermia, common symptoms of FA. In the gut, GF mice expressed low levels of the MC tissue-homing markers CXCL1 and CXCL2 and harbored fewer MC which exhibited lower levels of MC protease-1 after challenge. Additionally, MC in GF mice were less mature as confirmed by flow-cytometry and reduced edema formation after injection of degranulation-provoking compound 48/80. Co-housing of GF mice with CV mice fully restored their susceptibility to develop FA. However, this did not occur when GF mice were mono-colonized with L. plantarum.Conclusion Our results demonstrate that microbiota-induced maturation and gut-homing of MC is a critical step for the development of symptoms of experimental FA. This new mechanistic insight into microbiota-MC-FA axis can be exploited in the prevention and treatment of FA in humans.Abbreviations usedCVConventionalExGFGF mice co-housed with conventional miceFAFood allergyGFGerm-freeILInterleukinLPSLipopolysaccharideMCMast cellsMCPT-1Mast cell protease-1OVAOvalbuminPCRPolymerase chain reactionSPFSpecific pathogen free