Pairwise Stimulations of Pathogen-Sensing Pathways Predict Immune Responses to Multi-adjuvant Combinations
Year: 2020
Type: article
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.
Source: Cell Systems
Authors: Surya Pandey, Adam Gruenbaum, Tamara Kanashova, Philipp Mertins, Philippe Cluzel, Nicolas Chevrier
Institutions: University of Chicago, Max Delbrück Center, Harvard University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,200
Funders: National Science Foundation, American Cancer Society, Melanoma Research Alliance, University of Chicago, National Institutes of Health, University of Chicago Medicine, National Cancer Institute, National Institute of Allergy and Infectious Diseases, Comprehensive Cancer Center, University of Chicago Medical Center
OpenAlex ID: W3095906253