New Insights into the Antimicrobial Effect of Mast Cells against Enterococcus faecalis

Abstract

c Enterococcus faecalis has emerged as an important cause of life-threatening multidrug-resistant bacterial infections in the hospital setting. The pathogenesis of enterococcal infections has remained a relatively neglected field despite their obvious clinical relevance. The objective of this study was to characterize the interactions between mast cells (MCs), an innate immune cell population abundant in the intestinal lamina propria, and E. faecalis. This study was conducted with primary bone marrow-derived murine MCs. The results demonstrated that MCs exerted an antimicrobial effect against E. faecalis that was mediated both by degranulation, with the concomitant discharge of the antimicrobial effectors contained in the granules, and by the release of extracellular traps, in which E. faecalis was snared and killed. In particular, the cathelicidin LL-37 released by the MCs had potent antimicrobial effect against E. faecalis. We also investigated the specific receptors involved in the recognition of E. faecalis by MCs. We found that Toll-like receptors (TLRs) are critically involved in the MC recognition of E. faecalis, since MCs deficient in the expression of MyD88, an adaptor molecule required for signaling by most TLRs, were significantly impaired in their capacity to degranulate, to reduce E. faecalis growth as well as to release tumor necrosis factor alpha (TNF-␣) and interleukin 6 (IL-6) after encountering this pathogen. Furthermore, TLR2 was identified as the most prominent TLR involved in the recognition of E. faecalis by MCs. The results of this study indicate that MCs may be important contributors to the host innate immune defenses against E. faecalis.

Roles of Mas-related G protein–coupled receptor X2 on mast cell–mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases

“…25, 72, 77 Enterococcus faecalis has emerged as an important cause of life-threatening multidrug-resistant bacterial infections in the hospital setting. Scheb-Wetzel et al, 78 recently showed that MCs exert potent antimicrobial effect against this pathogen and that this effect is mediated via their degranulation and release of LL-37. Moreover, LL-37 protects skin from necrotic skin infections and promotes healing.…”

Mast cells as protectors of health

“…Sensing of bacterial products and humoral factors of the innate immune system results in MC degranulation, with concomitant release of a wide selection of biological active antimicrobial compounds and proinflammatory cytokines and chemokines. [39][40][41][42] Consequently, MCs critically contribute to the host defense against invading bacteria through 2 modes of action: (1) direct antimicrobial effect and (2) recruitment and activation of inflammatory cells to the site of infection. For example, it has been reported that MC-mediated release of TNF promotes neutrophil recruitment to the site of Klebsiella pneumonia infection, 18 whereas secretion of cathelicidins by MCs has direct bactericidal effects on Streptococcus pyogenes.…”

“…For example, it has been reported that MC-mediated release of TNF promotes neutrophil recruitment to the site of Klebsiella pneumonia infection, 18 whereas secretion of cathelicidins by MCs has direct bactericidal effects on Streptococcus pyogenes. 43 In this context it has been shown that MCs undergo degranulation on TLR2-mediated sensing of Staphylococcus aureus 44 and Enterococcus faecalis, 39 resulting in release of granule mediators that are very efficient at inhibiting pathogen growth. Furthermore, S aureus d-toxininduced MC degranulation might be a major mechanism through which T H 2 skin inflammation is exacerbated in atopic lesions.…”

Modulation of host defense peptide-mediated human mast cell activation by LPS

“…24 Enterococcus faecalis has emerged as an important cause of life-threatening multidrug-resistant bacterial infections in the hospital setting. Scheb-Wetzel et al, 25 recently showed that mast cells exert potent antimicrobial effect against this pathogen and that this effect is mediated via mast cell degranulation and the release of CRAMP. Furthermore, CRAMP has been shown to protect skin from necrotic skin infection and to promote healing.…”