Detection of Bacterial Membrane Vesicles by NOD-Like Receptors

Ella L Johnston,Thomas A Kufer,Maria Kaparakis-Liaskos,Begoña Heras

doi:10.3390/ijms22031005

Ella L Johnston, Thomas A Kufer + Show 2 more

Open Access

https://doi.org/10.3390/ijms22031005

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Abstract

Bacterial membrane vesicles (BMVs) are nanoparticles produced by both Gram-negative and Gram-positive bacteria that can function to modulate immunity in the host. Both outer membrane vesicles (OMVs) and membrane vesicles (MVs), which are released by Gram-negative and Gram-positive bacteria, respectively, contain cargo derived from their parent bacterium, including immune stimulating molecules such as proteins, lipids and nucleic acids. Of these, peptidoglycan (PG) and lipopolysaccharide (LPS) are able to activate host innate immune pattern recognition receptors (PRRs), known as NOD-like receptors (NLRs), such as nucleotide-binding oligomerisation domain-containing protein (NOD) 1, NOD2 and NLRP3. NLR activation is a key driver of inflammation in the host, and BMVs derived from both pathogenic and commensal bacteria have been shown to package PG and LPS in order to modulate the host immune response using NLR-dependent mechanisms. Here, we discuss the packaging of immunostimulatory cargo within OMVs and MVs, their detection by NLRs and the cytokines produced by host cells in response to their detection. Additionally, commensal derived BMVs are thought to shape immunity and contribute to homeostasis in the gut, therefore we also highlight the interactions of commensal derived BMVs with NLRs and their roles in limiting inflammatory diseases.

Highlights

Bacterial membrane vesicles (BMVs) produced by commensal bacteria may promote gut homeostasis as a result of activation of nucleotide-binding oligomerisation domain-containing protein 1 (NOD1) and NOD2 in epithelial cells
BMVs produced by all bacteria are important activators of nucleotide-binding oligomerisation domain-containing protein (NOD)-like receptors (NLRs) responsible for mediating inflammatory responses that contribute to pathogenesis, along with facilitating immunoregulation within the host
NOD1 and promote pathogenesis, BMVs produced by pathogens have emerged as nanocarriers that function via a range of mechanisms to activate NLRs and promote disease

Summary

BMVs Contain a Range of Immunostimulatory Cargo

A number of bacterial species have been shown to release BMVs containing immunostimulatory cargo known as microbe-associated molecular patterns (MAMPs), which includes peptidoglycan (PG), lipopolysaccharide (LPS), DNA and RNA (Figure 1) [10,13,14,15,16,17]. BMVs produced by a range of pathogens could activate NOD1, for example H. pylori and P. aeruginosa OMVs were shown to enter host epithelial cells which were detected by NOD1, resulting in the recruitment of RIPK2 to early endosomes and the activation of autophagy in the host cell (Table 1, Figure 2A) [31]. Not all periodontal pathogens are able to activate NODs, as OMVs produced by the periodontal pathogen P. gingivalis could activate both NOD1 and NOD2 leading to NF-kB production, whereas OMVs produced by Treponema denticola and Tannerella forsythia could not mediate NOD1 or NOD2 activation [26] These studies highlight that a number of pathogens produce BMVs that are capable of delivering PG to the cytosol of host cells, where it is detected by NOD1 and NOD2, resulting in the activation of a proinflammatory response. Cell type- or bacterial species-dependent responses observed within each row

Autophagy Induced by Detection of BMVs by NLRs

Detection of Commensal Derived BMVs by NODs

Inflammasome Activation by BMVs

Conclusions