Interspecies Communication between Pathogens and Immune Cells via Bacterial Membrane Vesicles

Abstract

The production of extracellular vesicles is a universal mechanism for intercellular communication that is conserved across kingdoms. Prokaryotes secrete 50–250 nm membrane vesicles (MVs) in a manner that is regulated by environmental stress and is thought to promote survival. Since many types of host-derived stress are encountered during infection, this implies an important role for MV secretion in bacterial pathogenesis. Accordingly, MVs produced by gram-positive and gram-negative pathogens contain toxins, virulence factors, and other molecules that promote survival in the host. However, recent studies have also shown that bacterial MVs are enriched for molecules that stimulate innate and adaptive immune responses. As an example, MVs may serve multiple, important roles in regulating the host response to Mycobacterium tuberculosis (Mtb), an intracellular pathogen that infects lung macrophages and resides within modified phagosomes. Previously, we demonstrated that Mtb secretes MVs during infection that may modulate infected and uninfected immune cells. Our present data demonstrates that Mtb MVs inhibit the functions of macrophages and T cells, but promote Major Histocompatibility Complex (MHC) class II antigen presentation by dendritic cells. We conclude that bacterial MVs serve dual and opposing roles in the activation of and defense against host immune responses to Mtb and other bacterial pathogens. We also propose that MV secretion is a central mechanism for interspecies communication between bacteria and host cells during infection.

Extracellular membrane vesicles in the three domains of life and beyond

“…2017), allowing cells to secrete and share with other cells lipids, hydrophobic, leaderless or denatured proteins, or hydrophobic signaling molecules (for recent reviews, see Jurkoshek et al. 2016; Penfornis et al. 2016; Tkach and Théry 2016; Domingues and Nielsen 2017; Kouwaki et al.…”

Mycobacterial extracellular vesicles and host pathogen interactions

“… 2017 ), protein antigens to dendritic cells (Jurkoshek et al. 2016 ) and mycobactin-iron to neighboring bacteria (Prados-Rosales et al. 2014c ), but the mechanisms involved in MEV interactions with host or bacterial cells are unclear.…”

“…It was also found that MEVs containing immunodominant antigenic proteins could transfer antigens to dendritic cells for presentation to T-cells (Jurkoshek et al. 2016 ), suggesting that MEVs participate in immune stimulation. It has been demonstrated that EVs released by M. tuberculosis -infected macrophages constitute a mixture of macrophage-derived exosomes and MEVs (Athman et al.…”

Trafficking of Mycobacterium tuberculosis Envelope Components and Release Within Extracellular Vesicles: Host-Pathogen Interactions Beyond the Wall

“…Mouse bone marrow-derived macrophages (BMM) stimulated with purified BCG BMV produce IL-1β, IL-6, IL-12, TNF, CXCL1 in a TLR2-dependent way as well as MIP-1α and IL-10, independently of TLR2 ( 51 , 52 ). In addition, BMV are capable to deliver antigens to dendritic cells leading to T cells stimulation ( 61 ). In contrast, Mtb BMV were described as inhibiting CD4 + T cells activation in vitro ( 62 ) through the direct delivery of LAM, which has been previously shown to repress TCR signaling ( 63 ).…”