title: Listeria monocytogenes alters mast cell phenotype, mediator and osteopontin secretion in a listeriolysin-dependent manner.
abstract: Whilst mast cells participate in the immune defence against the intracellular bacterium Listeria monocytogenes, there is conflicting evidence regarding the ability of L. monocytogenes to infect mast cells. It is known that the pore-forming toxin listeriolysin (LLO) is important for mast cell activation, degranulation and the release of pro-inflammatory cytokines. Mast cells, however, are a potential source of a wide range of cytokines, chemokines and other mediators including osteopontin, which contributes to the clearing of L. monocytogenes infections in vivo, although its source is unknown. We therefore aimed to resolve the controversy of mast cell infection by L. monocytogenes and investigated the extent of mediator release in response to the bacterium. In this paper we show that the infection of bone marrow-derived mast cells by L. monocytogenes is inefficient and LLO-independent. LLO, however, is required for calcium-independent mast cell degranulation as well as for the transient and selective downregulation of cell surface CD117 (c-kit) on mast cells. We demonstrate that in addition to the key pro-inflammatory cytokines TNF-α and IL-6, mast cells release a wide range of other mediators in response to L. monocytogenes. Osteopontin, IL-2, IL-4, IL-13 and granulocyte macrophage colony-stimulating factor (GM-CSF), and chemokines including CCL2, CCL3, CCL4 and CCL5 are released in a MyD88-dependent manner. The wide range of mediators released by mast cells in response to L. monocytogenes may play an important role in the recruitment and activation of a variety of immune cells in vivo. The cocktail of mediators, however, is unlikely to skew the immune response to a particular effector response. We propose that mast cells provide a hitherto unreported source of osteopontin, and may provide an important role in co-ordinating the immune response during Listeria infection.
authors: Faculty of Human and Medical Sciences, University of Manchester, Manchester, United Kingdom.
authors: Catherine E
authors: CE
authors: Jobbings
authors: Hilary
authors: H
authors: Sandig
authors: Jayde K
authors: JK
authors: Whittingham-Dowd
authors: Ian S
authors: IS
authors: Roberts
authors: Silvia
authors: S
authors: Bulfone-Paus
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology; D001427:Bacterial Toxins / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology; D015820:Cadherins / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000494:pharmacology*; D006460:Hemolysin Proteins / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000382:microbiology; D007700:Kinetics; D008089:Listeria monocytogenes / Q000502:physiology*; D008088:Listeriosis / Q000382:microbiology / Q000473:pathology; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D050296:Microbial Viability / Q000187:drug effects; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism*; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D015820:Cadherins; D018932:Chemokine CCL2; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D015850:Interleukin-6; D053594:Myeloid Differentiation Factor 88; D053495:Osteopontin; C069761:internalin protein, Bacteria; D019009:Proto-Oncogene Proteins c-kit; C038705:hlyA protein, Listeria monocytogenes; D002118:Calcium