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Standardized Whole-Blood Transcriptional Profiling Enables the Deconvolution of Complex Induced Immune Responses

Alejandra Urrutia, Darragh Duffy, Vincent Rouilly, Céline Posseme, Raouf Djebali, Gabriel Illanes, Valentina Libri, Benoit Albaud, David Gentien, Barbara Piasecka, Milena Hasan, Magnus Fontes, Lluis Quintana-Murci, Milieu Interieur Consortium

The initiation of inflammatory responses is typically triggered by a local event engaging sentinel cells, leading to the subsequent recruitment and accumulation of leukocytes. This process can result in the elimination of the initial cause of tissue disruption, the clearance of dying cells, and establishes a path toward tissue resolution. Cytokines mediate cell-to-cell communication, acting to recruit immune cells to inflammatory microenvironment and drive the required effector mechanisms. Despite the inherent complexity of these processes in natura, analyses of inflammation have typically focused on the decision-making circuits within cells, and, in most cases, have been restricted to single cell types (Amit et al., 2009, Jovanovic et al., 2015, Lee et al., 2014). Several other studies have assessed in vivo responses to vaccination, typically performing sampling over time to assess induced protein, mRNA expression, and seroconversion (Banchereau et al., 2014, Li et al., 2014, Tsang et al., 2014). While informative, these latter approaches permit the testing of only one stimulation condition per individual and are restricted to qualified or experimental vaccines. To properly account for inter-individual variability in the deconvolution of complex immune responses, both simple (synthetic or purified ligand) and complex (live or heat-killed microbe), stimulations must be performed in the same donor and at the same time, and standardized approaches for all steps from sample collection to analysis must be applied.

The Milieu Intérieur study - an integrative approach for study of human immunological variance.

Thomas S, Rouilly V, Patin E, Alanio C, Dubois A, Delval C, Marquier LG, Fauchoux N, Sayegrih S, Vray M, Duffy D, Quintana-Murci L, Albert ML; for The Milieu Intérieur Consortium.

The Milieu Intérieur Consortium has established a 1,000-person healthy population-based study (stratified according to sex and age), creating an unparalleled opportunity for assessing the determinants of human immunologic variance. Herein, we define the criteria utilized for...


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anr.jpgInvestissements d'avenirInstitut Pasteur InsermCNRShotscreen_1.jpgMYRIAD RBMInstitut Curie Etude Nutrinet Santé  PARCC Université Paris 13 Nord Université Paris Diderot Paris 7lund_univ.gif   epfl.png