Exploring the versatile roles of the endocannabinoid system and phytocannabinoids in modulating bacterial infections

Infect Immun. 2024 Jun 11;92(6):e0002024. doi: 10.1128/iai.00020-24. Epub 2024 May 22.

Abstract

The endocannabinoid system (ECS), initially identified for its role in maintaining homeostasis, particularly in regulating brain function, has evolved into a complex orchestrator influencing various physiological processes beyond its original association with the nervous system. Notably, an expanding body of evidence emphasizes the ECS's crucial involvement in regulating immune responses. While the specific role of the ECS in bacterial infections remains under ongoing investigation, compelling indications suggest its active participation in host-pathogen interactions. Incorporating the ECS into the framework of bacterial pathogen infections introduces a layer of complexity to our understanding of its functions. While some studies propose the potential of cannabinoids to modulate bacterial function and immune responses, the outcomes inherently hinge on the specific infection and cannabinoid under consideration. Moreover, the bidirectional relationship between the ECS and the gut microbiota underscores the intricate interplay among diverse physiological processes. The ECS extends its influence far beyond its initial discovery, emerging as a promising therapeutic target across a spectrum of medical conditions, encompassing bacterial infections, dysbiosis, and sepsis. This review comprehensively explores the complex roles of the ECS in the modulation of bacteria, the host's response to bacterial infections, and the dynamics of the microbiome. Special emphasis is placed on the roles of cannabinoid receptor types 1 and 2, whose signaling intricately influences immune cell function in microbe-host interactions.

Keywords: 2-arachidonoylglycerol; anandamide; bacterial pathogens; cannabinoid receptors; endocannabinoid system; gut microbiota; host-pathogen interactions; innate immune cells; intracellular infections; macrophage polarization; phagocytosis; polymicrobial sepsis.

Publication types

  • Review

MeSH terms

  • Animals
  • Bacterial Infections* / immunology
  • Bacterial Infections* / microbiology
  • Cannabinoids* / metabolism
  • Cannabinoids* / pharmacology
  • Endocannabinoids* / metabolism
  • Gastrointestinal Microbiome*
  • Host-Pathogen Interactions* / immunology
  • Humans

Substances

  • Endocannabinoids
  • Cannabinoids