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Pneumolysin binds t...
Pneumolysin binds to the mannose receptor C type 1 (MRC-1) leading to anti-inflammatory responses and enhanced pneumococcal survival
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- Subramanian, Karthik (author)
- Karolinska Institutet
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- Neill, Daniel R. (author)
- Univ Liverpool, Inst Infect & Global Hlth, Liverpool, Merseyside, England.
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- Malak, Hesham A. (author)
- Karolinska Institutet
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- Spelmink, Laura (author)
- Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.
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- Khandaker, Shadia (author)
- Univ Liverpool, Inst Infect & Global Hlth, Liverpool, Merseyside, England.
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- Marchiori, Giorgia Dalla Libera (author)
- Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.
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- Dearing, Emma (author)
- Univ Liverpool, Inst Infect & Global Hlth, Liverpool, Merseyside, England.
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- Kirby, Alun (author)
- Univ York, Ctr Immunol & Infect, Dept Biol, York, N Yorkshire, England.;Univ York, Hull York Med Sch, York, N Yorkshire, England.
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- Yang, Marie (author)
- Univ Liverpool, Inst Infect & Global Hlth, Liverpool, Merseyside, England.
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- Achour, Adnane (author)
- Karolinska Inst, Dept Med Solna, Sci Life Lab, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Dept Infect Dis, Stockholm, Sweden.
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- Nilvebrant, Johan, 1982- (author)
- KTH,Proteinteknologi
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- Nygren, Per-Åke, 1961- (author)
- KTH,Proteinteknologi
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- Plant, Laura (author)
- Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.
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- Kadioglu, Aras (author)
- Univ Liverpool, Inst Infect & Global Hlth, Liverpool, Merseyside, England.
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- Henriques-Normark, Birgitta (author)
- Karolinska Institutet
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Karolinska Institutet Univ Liverpool, Inst Infect & Global Hlth, Liverpool, Merseyside, England (creator_code:org_t)
- 2018-11-12
- 2019
- English.
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In: Nature Microbiology. - : Nature Publishing Group. - 2058-5276. ; 4:1, s. 62-70
- Related links:
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Streptococcus pneumoniae (the pneumococcus) is a major cause of mortality and morbidity globally, and the leading cause of death in children under 5 years old. The pneumococcal cytolysin pneumolysin (PLY) is a major virulence determinant known to induce pore-dependent pro-inflammatory responses. These inflammatory responses are driven by PLY-host cell membrane cholesterol interactions, but binding to a host cell receptor has not been previously demonstrated. Here, we discovered a receptor for PLY, whereby pro-inflammatory cytokine responses and Toll-like receptor signalling are inhibited following PLY binding to the mannose receptor C type 1 (MRC-1) in human dendritic cells and mouse alveolar macrophages. The cytokine suppressor SOCS1 is also upregulated. Moreover, PLY-MRC-1 interactions mediate pneumococcal internalization into non-lysosomal compartments and polarize naive T cells into an interferon-gamma(low), interleukin-4(high) and FoxP3(+) immunoregulatory phenotype. In mice, PLY-expressing pneumococci colocalize with MRC-1 in alveolar macrophages, induce lower pro-inflammatory cytokine responses and reduce neutrophil infiltration compared with a PLY mutant. In vivo, reduced bacterial loads occur in the airways of MRC-1-deficient mice and in mice in which MRC-1 is inhibited using blocking antibodies. In conclusion, we show that pneumococci use PLY-MRC-1 interactions to downregulate inflammation and enhance bacterial survival in the airways. These findings have important implications for future vaccine design.
Subject headings
- NATURVETENSKAP -- Biologi -- Mikrobiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Microbiology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Subramanian, Kar ...
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Neill, Daniel R.
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Malak, Hesham A.
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Spelmink, Laura
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Khandaker, Shadi ...
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Marchiori, Giorg ...
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show more...
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Dearing, Emma
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Kirby, Alun
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Yang, Marie
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Achour, Adnane
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Nilvebrant, Joha ...
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Nygren, Per-Åke, ...
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Plant, Laura
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Kadioglu, Aras
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Henriques-Normar ...
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Microbiology
- Articles in the publication
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Nature Microbiol ...
- By the university
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Royal Institute of Technology
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Karolinska Institutet