Staphylococcus aureus Evades the Extracellular Antimicrobial Activity of Mast Cells by Promoting Its Own Uptake

Abel, Jens; Goldmann, Oliver; Ziegler, Christina; Höltje, Claudia; Smeltzer, Mark S.; Cheung, Ambrose L.; Bruhn, Daniela; Rohde, Manfred; Medina, Eva

doi:10.1159/000327714

Cited by 73 publications

(104 citation statements)

References 73 publications

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“…MCs have been shown to be able to kill bacteria by two different mechanisms (16): (i) phagocytosis (mainly Gram-negative bacteria) and/or (ii) extracellularly either by the release of antimicrobial peptides such as LL-37 by degranulation or by the formation of MCETs (17) or by a combination of both (18). We found no evidence that E. faecalis could actively invade MCs as was previously demonstrated for other Gram-positive pathogens, like Staphylococcus aureus (18), or Gram-negative bacteria, like Escherichia coli (32).…”

Section: Discussionmentioning

confidence: 99%

“…MCs were isolated and differentiated as previously described (18). Briefly, mice were sacrificed by CO 2 asphyxiation and the femurs and tibias were removed.…”

Section: Methodsmentioning

confidence: 99%

“…E. faecalis was added to wells containing BMMCs at a multiplicity of infection (MOI) of 1 bacterium per cell (1:1) or to wells containing medium alone. The MOI of 1:1 was chosen based on a previous report (18) to ensure optimal conditions for the investigation of extracellular killing mechanisms elicited by MCs. Kinetics of bacterial growth in the presence or absence of MCs was monitored at various time points of infection by determination of CFU in the cell cultures.…”

Section: Methodsmentioning

confidence: 99%

“…Despite their known role in the initiation of allergic reactions, chronic inflammatory processes, and activation during certain types of parasitic infections (13,14), there is now clear evidence that MCs also play a prominent role in the early immune response to invading pathogens (10,15). MCs can also contribute to host defense by exerting a direct antimicrobial effect against pathogens either through phagocytosis (16) or by releasing extracellular traps (MCETs), which are structures composed of DNA, histones, and granule proteins where the pathogens are snared and killed (17,18). After translocation through the intestinal barrier, E. faecalis comes most probably into contact with the MCs present beneath the intestinal epithelium.…”

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confidence: 99%

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

et al. 2014

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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.

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Section: Discussionmentioning

confidence: 99%

“…MCs were isolated and differentiated as previously described (18). Briefly, mice were sacrificed by CO 2 asphyxiation and the femurs and tibias were removed.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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

et al. 2014

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“…In many cases, PFTs impair immune defenses, and this is accomplished through several different mechanisms. These include allowing bacteria to physically hide from the immune system and survive phagocytosis (e.g., L. monocytogenes LLO [424,425], M. tuberculosis ESAT-6 [122], GBS ␤-h/c [361], S. aureus alpha-toxin [435], and C. perfringens PFO [92]), preventing the activation of immune pathways (e.g., complement activation by S. pneumoniae PLY [181] or inhibition of the IgG and IgM response by LLO during L. monocytogenes infection [383]), and preventing the actions of antimicrobial compounds (178,447).…”

Section: Disruption Of the Host Immune Responsementioning

confidence: 99%

Role of Pore-Forming Toxins in Bacterial Infectious Diseases

Los

Randis

Aroian

et al. 2013

Microbiol Mol Biol Rev

350

351

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SUMMARY Pore-forming toxins (PFTs) are the most common bacterial cytotoxic proteins and are required for virulence in a large number of important pathogens, including Streptococcus pneumoniae , group A and B streptococci, Staphylococcus aureus , Escherichia coli , and Mycobacterium tuberculosis . PFTs generally disrupt host cell membranes, but they can have additional effects independent of pore formation. Substantial effort has been devoted to understanding the molecular mechanisms underlying the functions of certain model PFTs. Likewise, specific host pathways mediating survival and immune responses in the face of toxin-mediated cellular damage have been delineated. However, less is known about the overall functions of PFTs during infection in vivo . This review focuses on common themes in the area of PFT biology, with an emphasis on studies addressing the roles of PFTs in in vivo and ex vivo models of colonization or infection. Common functions of PFTs include disruption of epithelial barrier function and evasion of host immune responses, which contribute to bacterial growth and spreading. The widespread nature of PFTs make this group of toxins an attractive target for the development of new virulence-targeted therapies that may have broad activity against human pathogens.

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Human mast cells exhibit an individualized pattern of antimicrobial responses

Garcia-Rodriguez

Bahri

Sattentau

et al. 2020

Immunity Inflam & Disease

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Introduction: Mast cells (MCs) are tissue-resident immune cells implicated in antibacterial responses. These include chemokine secretion, degranulation, and the release of mast cell-extracellular traps, which are primarily dependent on reactive oxygen species (ROS) production. Our study investigated whether human mast cells (hMCs) develop individual response patterns to bacteria located at different tissue sites: Escherichia coli (gut commensal), Listeria monocytogenes (foodborne intracellular pathogen), Staphylococcus aureus (skin commensal and opportunistic pathogen), and Streptococcus pneumoniae (upper respiratory tract commensal and lung pathogen). Methods: After live bacteria exposure, hMCs were analyzed by a combined flow cytometry assay for degranulation, ROS production, DNA externalization, and for β-hexosaminidase, chemokine, and prostaglandin release. Results: L. monocytogenes induced hMC degranulation, IL-8 and MCP-1 release coupled with DNA externalization in a novel hMC ROS independent manner. In contrast, S. pneumoniae caused ROS production without DNA release and degranulation. E. coli induced low levels of hMC degranulation combined with interleukin 8 and MCP-1 secretion and in the absence of ROS and DNA externalization. Finally, S. aureus induced hMCs prostaglandin D2 release and DNA release selectively. Our findings demonstrate a novel hMC phenomenon of DNA externalization independent of ROS production. We also showed that ROS production, degranulation, DNA externalization, and mediator secretion occur as independent immune reactions in hMCs upon bacterial encounter and that hMCs contribute to bacterial clearance.

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Staphylococcus aureus Evades the Extracellular Antimicrobial Activity of Mast Cells by Promoting Its Own Uptake

Cited by 73 publications

References 73 publications

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

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

Role of Pore-Forming Toxins in Bacterial Infectious Diseases

Human mast cells exhibit an individualized pattern of antimicrobial responses

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