High-throughput screening of caterpillars as a platform to study host–microbe interactions and enteric immunity Journal Article

   

Authors:	Windfelder, A. G.; Müller, F. H. H.; Mc Larney, B.; Hentschel, M.; Böhringer, A. C.; von Bredow, C. R.; Leinberger, F. H.; Kampschulte, M.; Maier, L.; von Bredow, Y. M.; Flocke, V.; Merzendorfer, H.; Krombach, G. A.; Vilcinskas, A.; Grimm, J.; Trenczek, T. E.; Flögel, U.
Article Title:	High-throughput screening of caterpillars as a platform to study host–microbe interactions and enteric immunity
Abstract:	Mammalian models of human disease are expensive and subject to ethical restrictions. Here, we present an independent platform for high-throughput screening, using larvae of the tobacco hornworm Manduca sexta, combining diagnostic imaging modalities for a comprehensive characterization of aberrant phenotypes. For validation, we use bacterial/chemical-induced gut inflammation to generate a colitis-like phenotype and identify significant alterations in morphology, tissue properties, and intermediary metabolism, which aggravate with disease progression and can be rescued by antimicrobial treatment. In independent experiments, activation of the highly conserved NADPH oxidase DUOX, a key mediator of gut inflammation, leads to similar, dose-dependent alterations, which can be attenuated by pharmacological interventions. Furthermore, the developed platform could differentiate pathogens from mutualistic gastrointestinal bacteria broadening the scope of applications also to microbiomics and host-pathogen interactions. Overall, larvae-based screening can complement mammals in preclinical studies to explore innate immunity and host-pathogen interactions, thus representing a substantial contribution to improve mammalian welfare. © 2022, The Author(s).
Journal Title:	Nature Communications
Volume:	13
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Date Published:	2022-11-24
Start Page:	7216
Language:	English
DOI:	10.1038/s41467-022-34865-7
PROVIDER:	scopus
PUBMED:	36433960
PMCID:	PMC9700799
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85142520561&doi=10.1038%2fs41467-022-34865-7&partnerID=40&md5=a15c734cf938f1dcac9817da5ae69cc1
Notes:	Article -- Export Date: 1 December 2022 -- Source: Scopus

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