TLR-exosomes exhibit distinct kinetics and effector function

TL;DR

This study reveals that TLR-stimulated exosomes can activate immune responses at a distance, with distinct kinetics and functions, including in vivo macrophage polarization and neutrophil recruitment, highlighting their role in immune communication.

Contribution

It is the first to demonstrate that TLR-exosomes can induce in vivo macrophage polarization and have distinct trafficking and effector functions compared to control exosomes.

Findings

TLR-exosomes can recapitulate TLR activation in distal cells.

RNA is essential for exosome effector function, as shown by UV abrogation.

TLR-exosomes induce macrophage M1 polarization and recruit neutrophils in vivo.

Abstract

The innate immune system is vital to rapidly responding to pathogens and Toll-like receptors (TLRs) are a critical component of this response. Nanovesicular exosomes play a role in immunity, but to date their exact contribution to the dissemination of the TLR response is unknown. Here we show that exosomes from TLR stimulated cells (TLR-exosomes) can largely recapitulate TLR activation in distal cells in vitro. We can abrogate the action-at-a-distance signaling of exosomes by UV irradiation, demonstrating that RNA is crucial for their effector function. We are the first to show that exosomes derived from poly(I:C) stimulated cells induce in vivo macrophage M1-like polarization within murine lymph nodes. These TLR-exosomes demonstrate enhanced trafficking to the node and preferentially recruit neutrophils as compared to control-exosomes. This work definitively establishes the differential effector function for TLR-exosomes in communicating the activation state of the cell of origin.