Cellular Metabolism Constrains Innate Immune Responses in Early Human Ontogeny
This week we profile a recent publication in Nature Communications from the laboratory of Dr.
Pascal Lavoie (pictured, back row, right) at the BC Children’s Hospital Research Institute and UBC.
Can you provide a brief overview of your lab’s current research focus?
The Lavoie Lab focuses on the development of the immune system in humans, from the third trimester of gestation throughout the neonatal period. We aim to characterize mechanisms of regulation of immune functions and how it affects health complications in newborns, especially those born prematurely, including inflammatory lung disease and sepsis (severe infections). The methods we employ to achieve these goals are a mix of epidemiology, clinical research (including interventions), primary cell immunology, genetics as well as systems level “-omics” (transcriptome, epigenome).
What is the significance of the findings in this publication?
In this publication by Kan, B., Michalski, C., et al., in Nature Communications, we pinpointed how innate immune responses are turned off during gestation. We have known for many years that these first-line responses, which are crucial to fight microbes, are turned off in early gestation. However, we did not know how. Studying monocytes from premature babies born at less than 33 weeks, we found that cells lack the capacity to rapidly increase glycolytic energy production required at the initiation of an inflammatory responses. These cells also lack protein synthesis capacity and are thus unable to produce key proteins involved in the immune response. Finally, we show that this mechanism greatly impairs the ability of preterm immune cells to detect the fungus microorganism Candida species, which is an important cause of severe infection in premature babies.
What are the next steps for this research?
Our next steps are to understand how immune cells develop and acquire the capacity to respond to microbes during the critical period when these babies are at highest risk of infection, and hopefully develop pre-clinical therapeutic protocols to metabolically reprogram and restore immune functions in neonatal immune cells in order to reduce preterm newborns vulnerability to infections.
This research was funded by:
This research was funded by the Canadian Institutes of Health Research, the BC Children’s Hospital Research Institute and the Michael Smith Foundation for Health Research (salary award to P Lavoie). We are also thankful to participating families who donated cord blood, the BC Women’s Hospital and BC Children’s Hospital Biobank for their support to the Premiee Biobank through which biological samples were collected for this study.