Schwarzer, M. | Search bioRxiv

bioRxiv2018

Germ-free mice exhibit mast cells with impaired functionality and gut homing and do not develop food allergy

BackgroundMucosal 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.\n\nObjectiveWe tested the hypothesis that commensal bacteria are essential for MC migration to the gut and their maturation impacting the susceptibility to FA.\n\nMethodsThe 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.\n\nResultsSystemic 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.\n\nConclusionOur 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.

immunology↗

bioRxiv2017

D-Alanine esterification of teichoic acids contributes to Lactobacillus plantarum mediated intestinal peptidase expression and Drosophila growth promotion upon chronic undernutrition

The microbial environment influence animal physiology. However, the underlying molecular mechanisms of such functional interactions are largely undefined. Previously, we showed that upon chronic undernutrition, strains of Lactobacillus plantarum, a dominant commensal partner of Drosophila, promote host juvenile growth and maturation partly via enhanced expression of intestinal peptidases. By screening a transposon insertion library of Lactobacillus plantarum in gnotobiotic Drosophila larvae, we identify a bacterial cell wall modifying machinery encoded by the pbpX2-dltXABCD operon that is critical to enhance host digestive capabilities and promote growth and maturation. Deletion of this operon leads to bacterial cell wall alteration with a complete loss of teichoic acids D-alanylation. We thus conclude that teichoic acids modifications participate in commensal-host interactions and specifically, D-alanine esterification of teichoic acids contributes to optimal L. plantarum mediated intestinal peptidase expression and Drosophila juvenile growth upon chronic undernutrition.\n\nHighlights- LpNC8 mutant library screening identifies genes affecting Drosophila growth promotion.\n- pbpX2-dlt operon is required for D-alanylation of teichoic acids and Drosophila growth.\n- Deleting the pbpX2-dlt operon alters host intestinal peptidase expression.\n- Peptidoglycan and pbpX2-dlt dependent signals are required for LpNC8 mediated growth promotion.\n\n\neTOC blurbAnimals establish interactions with their microbial communities that shape many aspects of their physiology including juvenile growth. However, the underlying molecular mechanisms are largely undefined. Matos et al. reveal that bacterial teichoic acids modifications contribute to host juvenile growth promotion.

microbiology↗