NDLI: Enhanced, Sialoadhesin-Dependent Uptake of Guillain-Barré Syndrome-Associated Campylobacter jejuni Strains by Human Macrophages

Content Provider	PubMed Central
Author	Heikema, Astrid P. Koning, Roman I. Rico, Sharon Duarte Dos Santos Rempel, Hans Jacobs, Bart C. Endtz, Hubert P. Van, Wamel Willem J. B. Samsom, Janneke N.
Editor	Flynn, J. L.
Copyright Year	2013
Abstract	Molecular mimicry between Campylobacter jejuni sialylated lipooligosaccharides (LOS) and human nerve gangliosides can trigger the production of cross-reactive antibodies which induce Guillain-Barré syndrome (GBS). To better understand the immune events leading to GBS, it is essential to know how sialylated LOS are recognized by the immune system. Here, we show that GBS-associated C. jejuni strains bind to human sialoadhesin (hSn), a conserved, mainly macrophage-restricted I-type lectin. Using hSn-transduced THP-1 cells, we observed that C. jejuni strains with α(2,3)-sialylated LOS, including strains expressing GM1a- and GD1a-like epitopes, bind to hSn. This observation is of importance, as these epitopes are frequently the targets of the cross-reactive antibodies detected in GBS patients. Interestingly, the Sn binding domains were not constitutively exposed on the surface of C. jejuni. Heat inactivation and the environmental conditions which food-borne C. jejuni encounters during its passage through the intestinal tract, such as low pH and contact with bile constituents, exposed LOS and facilitated Sn binding. Sn binding enhanced bacterial uptake and increased the production of interleukin-6 (IL-6) by primary human Sn-expressing monocyte-derived macrophages compared to control conditions, where Sn was blocked using neutralizing antibodies or when nonsialylated C. jejuni was used. Sn-mediated uptake has been reported to enhance humoral immune responses. As C. jejuni strains expressing ganglioside mimics GD1a and GM1a are closely associated with GBS, Sn binding may be a determining event in the production of cross-reactive antibodies and the development of GBS.
Related Links	http://dx.doi.org/10.1128/IAI.01437-12
Ending Page	2103
Page Count	9
Starting Page	2095
File Format	PDF
ISSN	10985522
e-ISSN	10985522
Journal	Infection and Immunity
Issue Number	6
Volume Number	81
Language	English
Publisher	American Society for Microbiology
Publisher Date	2013-06-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Parasitology Immunology Microbiology

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