title: Reduced Innate Immune Response to aStaphylococcus aureusSmall Colony Variant Compared to Its Wild-Type Parent Strain.
abstract: Background:Staphylococcus aureus (S. aureus)small colony variants (SCVs) can survive within the host intracellular milieu and are associated with chronic relapsing infections. However, it is unknown whether host invasion rates and immune responses differ between SCVs and their wild-type counterparts. This study used a stableS. aureusSCV (WCH-SK2SCV) developed from a clinical isolate (WCH-SK2WT) in inflammation-relevant conditions. Intracellular infection rates as well as host immune responses to WCH-SK2WTand WCH-SK2SCVinfections were investigated.Method:NuLi-1 cells were infected with either WCH-SK2WTor WCH-SK2SCV, and the intracellular infection rate was determined over time. mRNA expression of cells infected with each strain intra- and extra-cellularly was analyzed using a microfluidic qPCR array to generate an expression profile of thirty-nine genes involved in the host immune response.Results:No difference was found in the intracellular infection rate between WCH-SK2WTand WCH-SK2SCV. Whereas, extracellular infection induced a robust pro-inflammatory response, intracellular infection elicited a modest response. Intracellular WCH-SK2WTinfection induced mRNA expression ofTLR2, pro-inflammatory cytokines (IL1B, IL6, andIL12) and tissue remodeling factors (MMP9). In contrast, intracellular WCH-SK2SCVinfection induced up regulation of onlyTLR2.Conclusions:Whereas, host intracellular infection rates of WCH-SK2SCVand WCH-SK2WTwere similar, WCH-SK2SCVintracellular infection induced a less widespread up regulation of pro-inflammatory and tissue remodeling factors in comparison to intracellular WCH-SK2WTinfection. These findings support the current view that SCVs are able to evade host immune detection to allow their own survival.
authors.affiliation: Department of Surgery-Otorhinolaryngology Head and Neck Surgery, Basil Hetzel Institute, The University of Adelaide Adelaide, SA, Australia.
authors.forename: Judy J J
authors.initials: JJ
authors.lastname: Ou
authors.affiliation: Department of Surgery-Otorhinolaryngology Head and Neck Surgery, Basil Hetzel Institute, The University of Adelaide Adelaide, SA, Australia.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Drilling
authors.affiliation: Department of Surgery-Otorhinolaryngology Head and Neck Surgery, Basil Hetzel Institute, The University of Adelaide Adelaide, SA, Australia.
authors.forename: Clare
authors.initials: C
authors.lastname: Cooksley
authors.affiliation: Department of Surgery-Otorhinolaryngology Head and Neck Surgery, Basil Hetzel Institute, The University of Adelaide Adelaide, SA, Australia.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Bassiouni
authors.affiliation: School of Biological Sciences, Research Centre for Infectious Disease, The University of Adelaide Adelaide, SA, Australia.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Kidd
authors.affiliation: Department of Surgery-Otorhinolaryngology Head and Neck Surgery, Basil Hetzel Institute, The University of Adelaide Adelaide, SA, Australia.
authors.forename: Alkis J
authors.initials: AJ
authors.lastname: Psaltis
authors.affiliation: Department of Surgery-Otorhinolaryngology Head and Neck Surgery, Basil Hetzel Institute, The University of Adelaide Adelaide, SA, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wormald
authors.affiliation: Department of Surgery-Otorhinolaryngology Head and Neck Surgery, Basil Hetzel Institute, The University of Adelaide Adelaide, SA, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Vreugde
mesh_terms: D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology*; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D060888:Real-Time Polymerase Chain Reaction; D013211:Staphylococcus aureus / Q000276:immunology* / Q000502:physiology*
keywords: Staphylococcus aureus; epithelial cells; innate immune response; small colony variant; tissue remodeling