Extracellular Vesicles in Airway Homeostasis and Pathophysiology

Abstract

The epithelial–mesenchymal trophic unit (EMTU) is a morphofunctional entity involved in the maintenance of the homeostasis of airways as well as in the pathogenesis of several diseases, including asthma and chronic obstructive pulmonary disease (COPD). The “muco-microbiotic layer” (MML) is the innermost layer of airways made by microbiota elements (bacteria, viruses, archaea and fungi) and the surrounding mucous matrix. The MML homeostasis is also crucial for maintaining the healthy status of organs and its alteration is at the basis of airway disorders. Nanovesicles produced by EMTU and MML elements are probably the most important tool of communication among the different cell types, including inflammatory ones. How nanovesicles produced by EMTU and MML may affect the airway integrity, leading to the onset of asthma and COPD, as well as their putative use in therapy will be discussed here.

Biogenesis and Biological Functions of Extracellular Vesicles in Cellular and Organismal Communication With Microbes

“…The relationships among these organisms and with their hosts can range across all forms of symbiosis from parasitism, competition and commensalism to mutualism (Tyler, 2009). EVs are rapidly emerging as key players in the communications and physiological interactions among these microbes and their hosts (Woith et al, 2019;Caruana and Walper, 2020;Munhoz da Rocha et al, 2020;Cai et al, 2021;Díaz-Garrido et al, 2021a,b;Fucarino et al, 2021;Qiao et al, 2021 ; Figures 5, 6 and Table 2). These roles can include nutrition, virulence, predation, host defense, immuno-regulation, developmental signaling and environmental modification.…”

“…The identification of bacterial small RNAs as host-signaling molecules during nodulation of soybean by Bradyrhizobium japonicum (Ren et al, 2019) also suggests the involvement of BEVs as potential carriers of those RNAs. The contributions of EVs to microbiome-host interactions have been studied in particular detail in the context of the bacterial members of mammalian microbiomes (Ñahui Palomino et al, 2021), especially those of the mammalian gut (reviewed in detail by Díaz-Garrido et al, 2021a,b) and airways (reviewed by Fucarino et al, 2021). In the gut, a dense inner layer of mucus separates the host epithelial cells from the microbial community, while a looser outer layer of mucus serves as a matrix that is colonized by the microbes.…”

“…In mammalian airways, as in the gut, host EVs play critical roles in maintaining a healthy balance of immunological activities within the mucosa and its associated mucus layer (Fucarino et al, 2021). This balance can be disrupted by external factors such as allergens and tobacco smoke, resulting in asthma and chronic pulmonary obstructive disease (COPD).…”

“…Furthermore, study of BEVs produced by probiotic bacteria, such as E. coli Nissle 1917 (EcN) (Cañas et al, 2016) and kefir Lactobacillus strains (Seo et al, 2018) demonstrated that BEVs produced by these strains could reduce the increased expression of pro-inflammatory cytokines and down-regulate enzymes associated with injury and inflammation (Díaz-Garrido et al, 2021b). Associations of host EVs with airway pathologies present in asthma and COPD have also been extensively documented (reviewed in Fucarino et al, 2021). While EVs may be expected to play similar key roles in the interaction of plants with their microbiomes, this research area is still in its infancy (Motaung and Steenkamp, 2021).…”

Cargo exchange between human and bacterial extracellular vesicles in gestational tissues: a new paradigm in communication and immune development

“…Both human and bacterial-derived EVs are widely studied, although often exclusively. Human body sites (mouth, gut, skin, respiratory, and genital tracts), where host cells co-exist with bacterial species (microbiota) in a dynamic mutualistic relationship (microbiome) [2,[16][17][18][19][20][21][22][23][24] , are sources of EVs from both humans and microbes. The host-bacteria and bacteria-bacteria interactions at such niches can be mediated by the exchange of biomolecules between both cell types, some of which are packaged and transported by EVs in a paracrine fashion [2,16,25,26] .…”