title: Staphylococcus aureus evades the extracellular antimicrobial activity of mast cells by promoting its own uptake.
abstract: In this study, we investigated the interactions of Staphylococcus aureus with mast cells, which are multifunctional sentinels lining the surfaces of the body. We found that bone marrow-derived murine mast cells (BMMC) exerted a powerful phagocytosis-independent antimicrobial activity against S. aureus. Both the release of extracellular traps as well as discharge of antimicrobial compounds were the mechanisms used by the BMMC to kill extracellular S. aureus. This was accompanied by the secretion of mediators such as TNF-α involved in the recruitment of effector cells. Interestingly, S. aureus subverted the extracellular antimicrobial activity of the BMMC by internalizing within these cells. S. aureus was also capable to internalize within human mast cells (HMC-1) and within murine skin mast cells during in vivo infection. Bacteria internalization was, at least in part, mediated by the α5β1 integrins expressed on the surface of the mast cell. In the intracellular milieu, the bacterium survived and persisted by increasing the cell wall thickness and by gaining access into the mast cell cytosol. The expression of α-hemolysin was essential for staphylococci intracellular persistence. By hiding within the long-life mast cells, staphylococci not only avoid clearance but also establish an infection reservoir that could contribute to chronic carriage.
authors.affiliation: Infection Immunology Research Group, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Abel
authors.forename: Oliver
authors.initials: O
authors.lastname: Goldmann
authors.forename: Christina
authors.initials: C
authors.lastname: Ziegler
authors.forename: Claudia
authors.initials: C
authors.lastname: Höltje
authors.forename: Mark S
authors.initials: MS
authors.lastname: Smeltzer
authors.forename: Ambrose L
authors.initials: AL
authors.lastname: Cheung
authors.forename: Daniela
authors.initials: D
authors.lastname: Bruhn
authors.forename: Manfred
authors.initials: M
authors.lastname: Rohde
authors.forename: Eva
authors.initials: E
authors.lastname: Medina
mesh_terms: D000818:Animals; D017209:Apoptosis; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D002353:Carrier State / Q000276:immunology / Q000382:microbiology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004197:Disease Reservoirs / Q000382:microbiology; D004705:Endocytosis / Q000276:immunology; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology; D013211:Staphylococcus aureus / Q000472:pathogenicity / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D039081:Integrin alpha5beta1; D014409:Tumor Necrosis Factor-alpha; C021091:staphylococcal alpha-toxin