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Staphylococcus aureus Lipoprotein Induces Skin Inflammation, Accompanied with IFN-?-Producing T Cell Accumulation through Dermal Dendritic Cells.

ABSTRACT: Staphylococcus aureus (S. aureus) is a commensal bacteria on the human skin, which causes serious skin inflammation. Several immune cells, especially effector T cells (Teff), have been identified as key players in S. aureus-derived skin inflammation. However, the bacterial component that induces dramatic host immune responses on the skin has not been well characterized. Here, we report that S. aureus lipoprotein (SA-LP) was recognized by the host immune system as a strong antigen, so this response induced severe skin inflammation. SA-LP activated dendritic cells (DCs), and this activation led to Teff accumulation on the inflamed skin in the murine intradermal (ID) injection model. The skin-accumulated Teff pool was established by IFN-?-producing CD4? and CD8?T (Th1 and Tc1). SA-LP activated dermal DC (DDC) in a dominant manner, so that these DCs were presumed to possess the strong responsibility of SA-LP-specific Teff generation in the skin-draining lymph nodes (dLN). SA-LP activated DC transfer into the mice ear, which showed similar inflammation, accompanied with Th1 and Tc1 accumulation on the skin. Thus, we revealed that SA-LP has a strong potential ability to establish skin inflammation through the DC-Teff axis. This finding provides novel insights not only for therapy, but also for the prevention of S. aureus-derived skin inflammation.

SUBMITTER: Saito S

PROVIDER: S-EPMC6161079 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Staphylococcus aureus Lipoprotein Induces Skin Inflammation, Accompanied with IFN-γ-Producing T Cell Accumulation through Dermal Dendritic Cells.

Saito Suguru S Quadery Ali F AF

Pathogens (Basel, Switzerland) 20180729 3

Staphylococcus aureus (S. aureus) is a commensal bacteria on the human skin, which causes serious skin inflammation. Several immune cells, especially effector T cells (Teff), have been identified as key players in S. aureus-derived skin inflammation. However, the bacterial component that induces dramatic host immune responses on the skin has not been well characterized. Here, we report that S. aureus lipoprotein (SA-LP) was recognized by the host immune system as a strong an ...[more]

PMID: 30060633

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Project description:PurposeThis study aims to characterize the wild-type staphylococcal enterotoxin A (SEA)-producing Staphylococcus aureus.Materials and methodsWe identified 29 wild-type sea-positive S. aureus isolates from dairy and meat samples, as well as from patients, measured the amount of SEA produced under favorable cultivation conditions using enzyme-linked immunosorbent assay and sea mRNA transcriptional level and investigated the phage type as well as genetic diversity by means of pulsed-field gel electrophoresis and multilocus sequence typing.ResultsAmong 29 sea-positive isolates, 22 were from food sources (including one outbreak case) and seven from clinical patients. Five enterotoxin gene profiles, namely, sea (14 isolates), sea+sec (9 isolates), sea+seb (4 isolates), sea+seb+sec (1 isolate) and sea+seb+sed (1 isolate), were identified. Multilocus sequence typing generated sequence type (ST)1 (13 isolates), ST6 (5 isolates), ST59 (3 isolates), ST239 (3 isolates), ST5 (2 isolates), ST188 (2 isolate) and ST15 (1 isolate). The amount of SEA per 108 colony-forming unit (CFU) after 24 h of incubation was 1.1-33.5 (mean, 8.74; SD, 7.7) ng/108 CFU. The amount of SEA per hour incubation in the log growth phase was 0.1-12.0 (mean, 2.37; SD, 3.06) ng/108 CFU. Overall, 54.2% of SEA was produced in the log growth phase. Both the transcriptional level of sea mRNA and the amount of SEA in the log growth phase correlated well with the amount of SEA after 24 h of cultivation. Four isolates, namely, SA-212, SA-217, SA-340 and SA-341, were categorized to be of high SEA production (877-1,109 ng/mL, 24 h). The total amount of SEA was mainly based on the amount of SEA in 108 CFU, not the relatively fixed bacterial cell counts (21.1-43×108 CFU/mL). Seven isolates from patients all carried the ФMu3A phage, whereas 21 of the 22 isolates from the environmental sources all carried the ФSa3ms phage.ConclusionThe present study exhibits varied SEA production capacity of the wild sea-positive S. aureus strains. An apparent boundary in phage types between strains from the clinical samples and strains from the environment was also identified.

Project description:Staphylococcus aureus gamma-hemolysin CB (HlgCB) is a core-genome-encoded pore-forming toxin that targets the C5a receptor, similar to the phage-encoded Panton-Valentine leucocidin (PVL). Absolute quantification by mass spectrometry of HlgCB in 39 community-acquired pneumonia (CAP) isolates showed considerable variations in the HlgC and HlgB yields between isolates. Moreover, although HlgC and HlgB are encoded on a single operon, their levels were dissociated in 10% of the clinical strains studied. To decipher the molecular basis for the variation in hlgCB expression and protein production among strains, different regulation levels were analyzed in representative clinical isolates and reference strains. Both the HlgCB level and the HlgC/HlgB ratio were found to depend on hlgC promoter activity and mRNA processing and translation. Strikingly, only one single nucleotide polymorphism (SNP) in the 5' untranslated region (UTR) of hlgCB mRNA strongly impaired hlgC translation in the USA300 strain, leading to a strong decrease in the level of HlgC but not in HlgB. Finally, we found that high levels of HlgCB synthesis led to mortality in a rabbit model of pneumonia, correlated with the implication of the role of HlgCB in severe S. aureus CAP. Taken together, this work illustrates the complexity of virulence factor expression in clinical strains and demonstrates a butterfly effect where subtle genomic variations have a major impact on phenotype and virulence. IMPORTANCE S. aureus virulence in pneumonia results in its ability to produce several virulence factors, including the leucocidin PVL. Here, we demonstrate that HlgCB, another leucocidin, which targets the same receptors as PVL, highly contributes to S. aureus virulence in pvl-negative strains. In addition, considerable variations in HlgCB quantities are observed among clinical isolates from patients with CAP. Biomolecular analyses have revealed that a few SNPs in the promoter sequences and only one SNP in the 5' UTR of hlgCB mRNA induce the differential expression of hlgCB, drastically impacting hlgC mRNA translation. This work illustrates the subtlety of regulatory mechanisms in bacteria, especially the sometimes major effects on phenotypes of single nucleotide variation in noncoding regions.

Dataset Information

Staphylococcus aureus Lipoprotein Induces Skin Inflammation, Accompanied with IFN-?-Producing T Cell Accumulation through Dermal Dendritic Cells.

Publications

Staphylococcus aureus Lipoprotein Induces Skin Inflammation, Accompanied with IFN-γ-Producing T Cell Accumulation through Dermal Dendritic Cells.

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