The commensal bacterium <i>Lactiplantibacillus plantarum</i> imprints innate memory-like responses in mononuclear phagocytes
Aize Pellón, Diego Barriales, Ainize Peña‐Cearra, Janire Castelo, Ainhoa Palacios, Nerea Lopez, Estíbaliz Atondo, Miguel Ángel Pascual‐Itoiz, Itziar Martín‐Ruiz, Leticia Sampedro, Monika González-Lopez, Laura Bárcena, Teresa Martín-Mateos, José María Landete, Rafael Prados-Rosales, Laura Plaza‐Vinuesa, Rosario Múñoz, Blanca de las Rivas, Juan M. Rodrı́guez, Edurne Berra, Ana M. Aransay, Leticia Abecia, José Luis Lavín, Héctor Rodrı́guez, Juan Anguíta
Abstract
Gut microbiota is a constant source of antigens and stimuli to which the resident immune system has developed tolerance. However, the mechanisms by which mononuclear phagocytes, specifically monocytes/macrophages, cope with these usually pro-inflammatory signals are poorly understood. Here, we show that innate immune memory promotes anti-inflammatory homeostasis, using as model strains of the commensal bacterium Lactiplantibacillus plantarum. Priming of monocytes/macrophages with bacteria, especially in its live form, enhances bacterial intracellular survival and decreases the release of pro-inflammatory signals to the environment, with lower production of TNF and higher levels of IL-10. Analysis of the transcriptomic landscape of these cells shows downregulation of pathways associated with the production of reactive oxygen species (ROS) and the release of cytokines, chemokines and antimicrobial peptides. Indeed, the induction of ROS prevents memory-induced bacterial survival. In addition, there is a dysregulation in gene expression of several metabolic pathways leading to decreased glycolytic and respiratory rates in memory cells. These data support commensal microbe-specific metabolic changes in innate immune memory cells that might contribute to homeostasis in the gut.