A new approach for deciphering complex immune responses

The response to infection is highly variable from one individual to another. The Milieu Intérieur
consortium, coordinated by Prof. Matthew Albert (Immunobiology of dendritic cells Unit, Institut
Pasteur / Inserm) and Dr Lluis Quintana-Murci (Human Evolutionary Genetics Unit, Institut Pasteur /
CNRS) seek to establish the parameters that characterize the immune system of healthy individuals
and its natural variability. In a study just published (August 25th) in Cell Reports, coauthored by
Magnus Fontes (Centre for Mathematical Sciences, Lund University and International Group for Data
Analysis, Institut Pasteur) and one of Qlucore’s founders, the researchers describe a new approach
for analyzing the inflammatory response at the gene expression level in blood samples from healthy
individuals, which reproduces the conditions of in-vivo stimulation. 

The striking result from this study is that the immune response to complex stimuli such as bacteria,
viruses, and fungi could be defined and distinguished based on a small number of genes that were
induced by 4 key immune proteins or cytokines. In particular as few as fourty-four genes, that were
identified by machine learning techniques, could explain the variance present within such diverse
immune responses. At a time of high-throughput sequencing approaches which create huge
challenges for data analysis and medical applications, this study suggests that simplified approaches
if properly targetted may provide more effective solutions with easier clinical translation. In addition,
the study highlights that the utilization of highly standardized techniques for all steps including
sample collection, sample preparation, and data analysis results in the generation of higher quality
and more informative data.

“We are excited by the results of this study which demonstrated that a
relatively small subset of identified genes could explain the variability in responses to different
complex immune stimuli” said Dr Darragh Duffy, immunologist and manager of the Milieu Interieur
consortium at Institut Pasteur, Paris.