Extracellular vesicles modulate host-microbe responses by altering TLR2 activity and phagocytosis

Area of Science:

• Microbiology
• Immunology
• Cell Biology

Background:

• Oral administration of Gram-positive bacteria, particularly Lactobacillus and Bifidobacterium species, is known to modulate immune function.
• The precise mechanisms underlying these immunomodulatory effects are not fully understood but may involve direct interactions with the intestinal epithelium and dendritic cells (DCs).

Purpose of the Study:

• To investigate the influence of serum extracellular vesicles (EVs) on the immune activation properties of Lactobacillus and Bifidobacterium species in vitro.
• To elucidate the role of EVs in modulating bacterial interactions with DCs and subsequent immune responses.

Main Methods:

• In vitro analysis of immune activation by Lactobacillus and Bifidobacterium species in the presence and absence of serum EVs.
• Assessment of Toll-like receptor (TLR) activity using specific TLR ligands.
• Evaluation of DC phagocytosis of bacteria and non-microbial substances.
• Measurement of DC cytokine release.

Main Results:

• Serum EVs differentially affected immune responses: Bifidobacterium-induced TLR2/6 activity was inhibited by EVs, while TLR2/1 and TLR4 responses were enhanced.
• EVs influenced bacterial aggregation and modified DC phagocytosis, enhancing uptake of Bifidobacterium breve but reducing Lactobacillus rhamnosus phagocytosis.
• EVs did not impair DC phagocytic capacity for non-microbial substances, indicating specific modulation of microbe-DC interactions.
• Combined effects of EVs on TLR activity and phagocytosis led to differential proinflammatory DC cytokine release depending on the bacterial species.

Conclusions:

• Extracellular vesicles play a significant, previously unrecognized role in host-microbe interactions, particularly concerning oral probiotics.
• EVs modulate immune responses not by directly affecting host cells, but by interacting with bacterial surfaces and associated molecular patterns.
• Understanding EV-microbe interactions is crucial for deciphering the mechanisms of probiotic action and maintaining gut immune homeostasis.