Sialylation of Campylobacter jejuni lipo-oligosaccharides: impact on phagocytosis and cytokine production in mice.
BACKGROUND: Guillain-Barré syndrome (GBS) is a post-infectious polyradiculoneuropathy, frequently associated with antecedent Campylobacter jejuni (C. jejuni) infection. The presence of sialic acid on C. jejuni lipo-oligosaccharide (LOS) is considered a risk factor for development of GBS as it crucia...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2012
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| _version_ | 1826286930805915648 |
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| author | Huizinga, R Easton, A Donachie, A Guthrie, J van Rijs, W Heikema, A Boon, L Samsom, J Jacobs, B Willison, H Goodyear, C |
| author_facet | Huizinga, R Easton, A Donachie, A Guthrie, J van Rijs, W Heikema, A Boon, L Samsom, J Jacobs, B Willison, H Goodyear, C |
| author_sort | Huizinga, R |
| collection | OXFORD |
| description | BACKGROUND: Guillain-Barré syndrome (GBS) is a post-infectious polyradiculoneuropathy, frequently associated with antecedent Campylobacter jejuni (C. jejuni) infection. The presence of sialic acid on C. jejuni lipo-oligosaccharide (LOS) is considered a risk factor for development of GBS as it crucially determines the structural homology between LOS and gangliosides, explaining the induction of cross-reactive neurotoxic antibodies. Sialylated C. jejuni are recognised by TLR4 and sialoadhesin; however, the functional implications of these interactions in vivo are unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigated the effects of bacterial sialylation on phagocytosis and cytokine secretion by mouse myeloid cells in vitro and in vivo. Using fluorescently labelled GM1a/GD1a ganglioside-mimicking C. jejuni strains and corresponding (Cst-II-mutant) control strains lacking sialic acid, we show that sialylated C. jejuni was more efficiently phagocytosed in vitro by BM-MΦ, but not by BM-DC. In addition, LOS sialylation increased the production of IL-10, IL-6 and IFN-β by both BM-MΦ and BM-DC. Subsequent in vivo experiments revealed that sialylation augmented the deposition of fluorescent bacteria in splenic DC, but not macrophages. In addition, sialylation significantly amplified the production of type I interferons, which was independent of pDC. CONCLUSIONS/SIGNIFICANCE: These results identify novel immune stimulatory effects of C. jejuni sialylation, which may be important in inducing cross-reactive humoral responses that cause GBS. |
| first_indexed | 2024-03-07T01:51:02Z |
| format | Journal article |
| id | oxford-uuid:9a18cb3b-c1ab-4567-942d-45bd56a15da2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:51:02Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:9a18cb3b-c1ab-4567-942d-45bd56a15da22022-03-27T00:18:59ZSialylation of Campylobacter jejuni lipo-oligosaccharides: impact on phagocytosis and cytokine production in mice.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9a18cb3b-c1ab-4567-942d-45bd56a15da2EnglishSymplectic Elements at Oxford2012Huizinga, REaston, ADonachie, AGuthrie, Jvan Rijs, WHeikema, ABoon, LSamsom, JJacobs, BWillison, HGoodyear, CBACKGROUND: Guillain-Barré syndrome (GBS) is a post-infectious polyradiculoneuropathy, frequently associated with antecedent Campylobacter jejuni (C. jejuni) infection. The presence of sialic acid on C. jejuni lipo-oligosaccharide (LOS) is considered a risk factor for development of GBS as it crucially determines the structural homology between LOS and gangliosides, explaining the induction of cross-reactive neurotoxic antibodies. Sialylated C. jejuni are recognised by TLR4 and sialoadhesin; however, the functional implications of these interactions in vivo are unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigated the effects of bacterial sialylation on phagocytosis and cytokine secretion by mouse myeloid cells in vitro and in vivo. Using fluorescently labelled GM1a/GD1a ganglioside-mimicking C. jejuni strains and corresponding (Cst-II-mutant) control strains lacking sialic acid, we show that sialylated C. jejuni was more efficiently phagocytosed in vitro by BM-MΦ, but not by BM-DC. In addition, LOS sialylation increased the production of IL-10, IL-6 and IFN-β by both BM-MΦ and BM-DC. Subsequent in vivo experiments revealed that sialylation augmented the deposition of fluorescent bacteria in splenic DC, but not macrophages. In addition, sialylation significantly amplified the production of type I interferons, which was independent of pDC. CONCLUSIONS/SIGNIFICANCE: These results identify novel immune stimulatory effects of C. jejuni sialylation, which may be important in inducing cross-reactive humoral responses that cause GBS. |
| spellingShingle | Huizinga, R Easton, A Donachie, A Guthrie, J van Rijs, W Heikema, A Boon, L Samsom, J Jacobs, B Willison, H Goodyear, C Sialylation of Campylobacter jejuni lipo-oligosaccharides: impact on phagocytosis and cytokine production in mice. |
| title | Sialylation of Campylobacter jejuni lipo-oligosaccharides: impact on phagocytosis and cytokine production in mice. |
| title_full | Sialylation of Campylobacter jejuni lipo-oligosaccharides: impact on phagocytosis and cytokine production in mice. |
| title_fullStr | Sialylation of Campylobacter jejuni lipo-oligosaccharides: impact on phagocytosis and cytokine production in mice. |
| title_full_unstemmed | Sialylation of Campylobacter jejuni lipo-oligosaccharides: impact on phagocytosis and cytokine production in mice. |
| title_short | Sialylation of Campylobacter jejuni lipo-oligosaccharides: impact on phagocytosis and cytokine production in mice. |
| title_sort | sialylation of campylobacter jejuni lipo oligosaccharides impact on phagocytosis and cytokine production in mice |
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