Investigating Non-Microbial Causes of Trained Innate Immunity

Overview of the Study

A recent study explored the possibility that non-microbial factors, particularly high-calorie diets, can induce trained innate immunity. This line of investigation arises from emerging evidence suggesting the innate immune system has the capacity for developing trained immunity, which involves reprogramming its cellular components to enhance protection against reinfection.

Research Focus and Methodology

Conducted by researchers in Germany and published in the journal Cell, the study aimed to determine if non-microbial inflammation could trigger trained immunity. Using inflammation-prone Ldlr-negative mice, the researchers subjected them to a high-calorie diet, which led to a widespread inflammatory response characterized by increased levels of immature innate immune cells known as granulocyte monocyte precursors (GMPs). Following a shift back to a high-fiber diet, the systemic inflammation was significantly reduced.

Findings on Immune Cell Reprogramming

Despite the reduction in overall inflammation, the GMPs exhibited reprogramming, demonstrating heightened responsiveness to both microbial and non-microbial stimuli. The study further revealed that Ldlr-negative mice lacking the Nlrp3 protein, integral to recognizing damaged cellular components and initiating inflammatory responses, did not undergo reprogramming or display inflammation in response to a high-calorie diet.

Implications of the Research

These findings indicate that trained immunity can indeed arise from non-microbial sources of inflammation, suggesting a potential dependency on the Nlrp3 protein. The absence of Nlrp3 appears to hinder the development of trained immunity associated with high-calorie diets. Consequently, targeting the Nlrp3 protein may offer therapeutic benefits for conditions exacerbated by innate immune responses.

Reference

Christ, A. et al. (2018). Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming. Cell DOI: https://doi.org/10.1016/j.cell.2017.12.013

Author

Written by Raishard Haynes, MBS