The Staphylococcus aureus lipoprotein SitC colocalizes with Toll-like receptor 2 (TLR2) in murine keratinocytes and elicits intracellular TLR2 accumulation

P Müller; M Müller-Anstett; J Wagener; Q Gao; S Kaesler; M Schaller; T Biedermann; F Götz

doi:10.1128/IAI.00538-10

The Staphylococcus aureus lipoprotein SitC colocalizes with Toll-like receptor 2 (TLR2) in murine keratinocytes and elicits intracellular TLR2 accumulation

P Müller, M Müller-Anstett, J Wagener, Q Gao, S Kaesler, M Schaller, T Biedermann, F Götz

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Abstract

SitC is one of the predominant lipoproteins in Staphylococcus aureus. Recently, SitC was shown to be capable of stimulating Toll-like receptor 2 (TLR2), but the mechanism of TLR2 activation by SitC has not been analyzed in detail so far. In this study, we purified C-terminally His-tagged SitC (SitC-His) from Staphylococcus aureus. SitC-His induced interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-a) release in human monocytes and also NF-¿B activation in TLR2-transfected HEK293 cells, indicating TLR2-specific activation. SitC not only induced a TLR2-dependent release of IL-6 in primary murine keratinocytes (MKs) but also induced intracellular accumulation of TLR2, which was time and concentration dependent. Cy2-labeled SitC-His colocalized specifically with TLR2 in MKs and was also internalized in TLR2 knockout MKs, suggesting a TLR2-independent uptake. Neither activation nor colocalization of SitC-His was observed with TLR4 or Nod2. The results show that the native lipoprotein SitC-His specifically colocalizes with TLR2, is internalized by host cells, induces proinflammatory cytokines, and triggers intracellular accumulation of TLR2.

Original language	English
Pages (from-to)	4243-4250
Number of pages	8
Journal	Infection and Immunity
Volume	78
Issue number	10
DOIs	https://doi.org/10.1128/IAI.00538-10
Publication status	Published - Oct 2010

Keywords

animals
bacterial proteins
cell line
cytokines
gene expression regulation, bacterial
humans
keratinocytes
lipoproteins
mice
mice, inbred C57BL
mice, knockout
Nod2 signaling adaptor protein
protein transport
specific pathogen-free organisms
Staphylococcus aureus
toll-like receptor 2

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@article{3189228683b14a5b986ec74b924e7214,

title = "The Staphylococcus aureus lipoprotein SitC colocalizes with Toll-like receptor 2 (TLR2) in murine keratinocytes and elicits intracellular TLR2 accumulation",

abstract = "SitC is one of the predominant lipoproteins in Staphylococcus aureus. Recently, SitC was shown to be capable of stimulating Toll-like receptor 2 (TLR2), but the mechanism of TLR2 activation by SitC has not been analyzed in detail so far. In this study, we purified C-terminally His-tagged SitC (SitC-His) from Staphylococcus aureus. SitC-His induced interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-a) release in human monocytes and also NF-¿B activation in TLR2-transfected HEK293 cells, indicating TLR2-specific activation. SitC not only induced a TLR2-dependent release of IL-6 in primary murine keratinocytes (MKs) but also induced intracellular accumulation of TLR2, which was time and concentration dependent. Cy2-labeled SitC-His colocalized specifically with TLR2 in MKs and was also internalized in TLR2 knockout MKs, suggesting a TLR2-independent uptake. Neither activation nor colocalization of SitC-His was observed with TLR4 or Nod2. The results show that the native lipoprotein SitC-His specifically colocalizes with TLR2, is internalized by host cells, induces proinflammatory cytokines, and triggers intracellular accumulation of TLR2.",

keywords = "animals, bacterial proteins, cell line, cytokines, gene expression regulation, bacterial, humans, keratinocytes, lipoproteins, mice, mice, inbred C57BL, mice, knockout, Nod2 signaling adaptor protein, protein transport, specific pathogen-free organisms, Staphylococcus aureus, toll-like receptor 2",

author = "P M{\"u}ller and M M{\"u}ller-Anstett and J Wagener and Q Gao and S Kaesler and M Schaller and T Biedermann and F G{\"o}tz",

year = "2010",

month = oct,

doi = "10.1128/IAI.00538-10",

language = "English",

volume = "78",

pages = "4243--4250",

journal = "Infection and Immunity",

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publisher = "American Society for Microbiology",

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T1 - The Staphylococcus aureus lipoprotein SitC colocalizes with Toll-like receptor 2 (TLR2) in murine keratinocytes and elicits intracellular TLR2 accumulation

AU - Müller, P

AU - Müller-Anstett, M

AU - Wagener, J

AU - Gao, Q

AU - Kaesler, S

AU - Schaller, M

AU - Biedermann, T

AU - Götz, F

PY - 2010/10

Y1 - 2010/10

N2 - SitC is one of the predominant lipoproteins in Staphylococcus aureus. Recently, SitC was shown to be capable of stimulating Toll-like receptor 2 (TLR2), but the mechanism of TLR2 activation by SitC has not been analyzed in detail so far. In this study, we purified C-terminally His-tagged SitC (SitC-His) from Staphylococcus aureus. SitC-His induced interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-a) release in human monocytes and also NF-¿B activation in TLR2-transfected HEK293 cells, indicating TLR2-specific activation. SitC not only induced a TLR2-dependent release of IL-6 in primary murine keratinocytes (MKs) but also induced intracellular accumulation of TLR2, which was time and concentration dependent. Cy2-labeled SitC-His colocalized specifically with TLR2 in MKs and was also internalized in TLR2 knockout MKs, suggesting a TLR2-independent uptake. Neither activation nor colocalization of SitC-His was observed with TLR4 or Nod2. The results show that the native lipoprotein SitC-His specifically colocalizes with TLR2, is internalized by host cells, induces proinflammatory cytokines, and triggers intracellular accumulation of TLR2.

AB - SitC is one of the predominant lipoproteins in Staphylococcus aureus. Recently, SitC was shown to be capable of stimulating Toll-like receptor 2 (TLR2), but the mechanism of TLR2 activation by SitC has not been analyzed in detail so far. In this study, we purified C-terminally His-tagged SitC (SitC-His) from Staphylococcus aureus. SitC-His induced interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-a) release in human monocytes and also NF-¿B activation in TLR2-transfected HEK293 cells, indicating TLR2-specific activation. SitC not only induced a TLR2-dependent release of IL-6 in primary murine keratinocytes (MKs) but also induced intracellular accumulation of TLR2, which was time and concentration dependent. Cy2-labeled SitC-His colocalized specifically with TLR2 in MKs and was also internalized in TLR2 knockout MKs, suggesting a TLR2-independent uptake. Neither activation nor colocalization of SitC-His was observed with TLR4 or Nod2. The results show that the native lipoprotein SitC-His specifically colocalizes with TLR2, is internalized by host cells, induces proinflammatory cytokines, and triggers intracellular accumulation of TLR2.

KW - animals

KW - bacterial proteins

KW - cell line

KW - cytokines

KW - gene expression regulation, bacterial

KW - humans

KW - keratinocytes

KW - lipoproteins

KW - mice

KW - mice, inbred C57BL

KW - mice, knockout

KW - Nod2 signaling adaptor protein

KW - protein transport

KW - specific pathogen-free organisms

KW - Staphylococcus aureus

KW - toll-like receptor 2

U2 - 10.1128/IAI.00538-10

DO - 10.1128/IAI.00538-10

M3 - Article

C2 - 20679445

SN - 1098-5522

VL - 78

SP - 4243

EP - 4250

JO - Infection and Immunity

JF - Infection and Immunity

IS - 10

ER -

The Staphylococcus aureus lipoprotein SitC colocalizes with Toll-like receptor 2 (TLR2) in murine keratinocytes and elicits intracellular TLR2 accumulation

Abstract

Keywords

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