title: Flagellin expression enhances Salmonella accumulation in TLR5-positive macrophages.
abstract: Recently, it has been reported that Salmonella secrete flagellin in response to host produced lysophospholipids. However, this monomer of the bacterial flagella activates Toll-like receptor 5 (TLR5) in the innate immune system. The objective of this study was to examine the role of flagellin expression during infection of species-specific macrophages (MPhi) which either expressed or lacked TLR5. Initially, TLR5-activity was confirmed in bovine MPhi using Salmonella typhimurium derived-flagellin. Within these cells, recombinant FliC induced a potent CXCL8 response when compared to the heterogeneous (FliC/FljB) form of purified flagellin. Furthermore, neither form of flagellin induced nitrite secretion which was subsequently detected after exposing bovine MPhi to LPS in the presence of IFN-gamma. Flagellin enhanced the accumulation of Salmonella enteritidis in TLR5-positive bovine and human MPhi which was independent of adhesion in bovine MPhi. In contrast, murine MPhis which lacked TLR5 were equally susceptible to hosting S. enteritidis, with or without flagellin. However, lack of flagellin in S. typhimurium marginally inhibited bacterial accumulation in bovine MPhi, where FljB and FliC compensated for the lack of each other. This study suggests that flagellin may be inducing TLR5-dependent internalisation mechanisms in Mcapital EF, Cyrillic which vary qualitatively between different species and Salmonella serotypes.
authors.affiliation: Molecular Immunology Group, Department for Pathology and Infectious Diseases, Royal Veterinary College, Hawkshead Campus, Hawkshead Lane, North Mymms, Hertfordshire AL9 7TA, United Kingdom.
authors.forename: H J
authors.initials: HJ
authors.lastname: Metcalfe
authors.forename: A
authors.initials: A
authors.lastname: Best
authors.forename: T
authors.initials: T
authors.lastname: Kanellos
authors.forename: R M
authors.initials: RM
authors.lastname: La Ragione
authors.forename: D
authors.initials: D
authors.lastname: Werling
mesh_terms: D000818:Animals; D002417:Cattle; D015169:Colony Count, Microbial; D005408:Flagellin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D007114:Immunization; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D012480:Salmonella Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012477:Salmonella enteritidis / Q000276:immunology* / Q000472:pathogenicity; D012486:Salmonella typhimurium / Q000276:immunology* / Q000472:pathogenicity; D013045:Species Specificity; D051198:Toll-Like Receptor 5 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D020298:U937 Cells
chemical_list: D016209:Interleukin-8; D008070:Lipopolysaccharides; D051198:Toll-Like Receptor 5; D014409:Tumor Necrosis Factor-alpha; D005408:Flagellin