The Extracellular Vesicles from the Commensal Staphylococcus Epidermidis ATCC12228 Strain Regulate Skin Inflammation in the Imiquimod-Induced Psoriasis Murine Model

Abstract

Extracellular vesicles (EVs) are evaginations of the cytoplasmic membrane, containing nucleic acids, proteins, lipids, enzymes, and toxins. EVs participate in various bacterial physiological processes. Staphylococcus epidermidis interacts and communicates with the host skin. S. epidermidis’ EVs may have an essential role in this communication mechanism, modulating the immunological environment. This work aimed to evaluate if S. epidermidis’ EVs can modulate cytokine production by keratinocytes in vitro and in vivo using the imiquimod-induced psoriasis murine model. S. epidermidis’ EVs were obtained from a commensal strain (ATC12228EVs) and a clinical isolated strain (983EVs). EVs from both origins induced IL-6 expression in HaCaT keratinocyte cultures; nevertheless, 983EVs promoted a higher expression of the pro-inflammatory cytokines VEGF-A, LL37, IL-8, and IL-17F than ATCC12228EVs. Moreover, in vivo imiquimod-induced psoriatic skin treated with ATCC12228EVs reduced the characteristic psoriatic skin features, such as acanthosis and cellular infiltrate, as well as VEGF-A, IL-6, KC, IL-23, IL-17F, IL-36γ, and IL-36R expression in a more efficient manner than 983EVs; however, in contrast, Foxp3 expression did not significantly change, and IL-36 receptor antagonist (IL-36Ra) was found to be increased. Our findings showed a distinctive immunological profile induction that is dependent on the clinical or commensal EV origin in a mice model of skin-like psoriasis. Characteristically, proteomics analysis showed differences in the EVs protein content, dependent on origin of the isolated EVs. Specifically, in ATCC12228EVs, we found the proteins glutamate dehydrogenase, ornithine carbamoyltransferase, arginine deiminase, carbamate kinase, catalase, superoxide dismutase, phenol-soluble β1/β2 modulin, and polyglycerol phosphate α-glucosyltransferase, which could be involved in the reduction of lesions in the murine imiquimod-induced psoriasis skin. Our results show that the commensal ATCC12228EVs have a greater protective/attenuating effect on the murine imiquimod-induced psoriasis by inducing IL-36Ra expression in comparison with EVs from a clinical isolate of S. epidermidis.

Interactions of Gram-Positive Bacterial Membrane Vesicles and Hosts: Updates and Future Directions

“…Gram-positive bacterial MVs may also play a role in various pathologies, including dermatological and viral diseases. Streptococcus epidermidis MVs show potential therapeutic value for psoriasis [ 109 ], while Lactobacillus druckerii MVs may have applications for hyperplastic scars [ 110 ]. In conclusion, Palomino et al demonstrated that MVs from vaginally isolated Lactobacillus inhibited the adhesion and entry of the HIV-1 virus into human T cells [ 111 ] ( Figure 4 ).…”

Bacterial Extracellular Vesicles in the Regulation of Inflammatory Response and Host-Microbe Interactions

“…Bacterial EVs have been shown to play an important role in producing anti-inflammatory cytokines or blocking the production of proinflammatory cytokines (15,(94)(95)(96)(97)(98). When stimulated with LPS from E. coli, HT-29 epithelial cells can produce the proinflammatory cytokine IL-8.…”

“…In contrast to S. aureus EVs, Staphylococcus epidermidis ATCC12228 EVs can reverse the production of proinflammatory cytokines IL-6, IL-23, and IL-17F in murine skin caused by imiquimod-induced psoriasis, an inflammatory skin disease (96). The underlying mechanism could potentially be associated with a decrease in IL-36, which is responsible for inflammatory responses from immune cells and other proinflammatory cytokines found in psoriasis (96). Similarly, Clostridium butyricum EVs can reduce the production of proinflammatory cytokines IL-6, TNF-α, and IL-1β in LPS-treated RAW264.7 cells by blocking the NF-κB and MAPK pathways (99).…”

IgY Antibodies as Biotherapeutics in Biomedicine

“…Bacteria have the capacity for autonomous replication and can secrete virulence factors, such as toxins, genetic material, and extracellular vesicles, which contain any of the abovementioned components, allowing them to colonize and proliferate in different human and animal cells and tissues [ 38 ]. In this context, IgY has been used as a therapeutic option since it can reduce and prevent bacterial colonization.…”

“…IgY has also been proposed for the diagnosis of infections caused by Staphylococcus aureus and to limit skin alterations caused by staphylococcal protein A (SpA), as IgY against SpA is being added to creams and cosmetics to prevent infection [ 46 ]. In addition, IgY has been proposed against bacteria such as Staphylococcus epidermidis , related to surgical nosocomial infections [ 38 , 47 ], and even against tuberculosis, managing to counteract the bacterial load of the respiratory tract and lungs [ 48 ].…”