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Pairwise stimulations of pathogen-sensing pathways predict immune responses to multi-adjuvant combinations

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Item Type:Article
Title:Pairwise stimulations of pathogen-sensing pathways predict immune responses to multi-adjuvant combinations
Creators Name:Pandey, S. and Gruenbaum, A. and Kanashova, T. and Mertins, P. and Cluzel, P. and Chevrier, N.
Abstract:The immune system makes decisions in response to combinations of multiple microbial inputs. We do not understand the combinatorial logic governing how higher-order combinations of microbial signals shape immune responses. Here, using coculture experiments and statistical analyses, we discover a general property for the combinatorial sensing of microbial signals, whereby the effects of triplet combinations of microbial signals on immune responses can be predicted by combining the effects of single and pairs. Mechanistically, we find that singles and pairs dictate the information signaled by triplets in mouse and human DCs at the levels of transcription, chromatin, and protein secretion. We exploit this simplifying property to develop cell-based immunotherapies prepared with adjuvant combinations that trigger protective responses in mouse models of cancer. We conclude that the processing of multiple input signals by innate immune cells is governed by pairwise effects, which will inform the rationale combination of adjuvants to manipulate immunity.
Keywords:Innate Immunity, Pattern-Recognition Receptors, Adjuvants, Cell Therapy, Cancer Immunotherapy, Animals, Mice
Source:Cell Systems
Publisher:Cell Press / Elsevier
Page Range:495-508
Date:18 November 2020
Official Publication:https://doi.org/10.1016/j.cels.2020.10.001
PubMed:View item in PubMed
Related to:
https://edoc.mdc-berlin.de/19128/Preprint version

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