The transcriptomic analytical level determines the human monocyte-derived macrophage response toward either the...

Macrophages exhibit multifunctional activity and play a central role in the response to infectious agents. It is commonly accepted that the plasticity of the response of macrophages depends on the type of stimuli. Here we re-evaluate whether the macrophage response is only dependent on the stimulus. We analyzed the transcriptomic profile of monocyte-derived macrophages (MDMs) that were activated with several pathogens and multiple in vitro-stimulations. The transcriptomic data were normalized using matched-pair analysis. Further analysis showed a clustering association with (i) specific signatures of the infectious agent and its strategy as well as (ii) a preponderance of MDM overall responses related to individuals. Currently, the null hypothesis H₀ is that the innate MDM response is globally associated with the pathogen. Our results reveal that the global innate MDM response is intrinsically and predominantly associated with the individual. Thus, the hypothesis is supported or negated depending on the transcriptomic analytical level.

In modern medicine, diagnosis is based on objective criteria. Scientists are focused on the common denominators indicative of an infection. Analytical studies are based on this oriented approach, which defines the null hypothesis H₀: the host immune response depends on the stimulus. We observe that the macrophage response to a given pathogen represents <0.4% of the expressed transcripts. The events to which the remaining 99.6% of transcripts are associated remain unclear. We find that 10.3% of the genes modulated during the response to the stimulus are related to the individual. They represent the overall response of the host, which integrates two responses: one associated with the stimulus and the other associated with the individual.