Enhanced, sialoadhesin-dependent uptake of guillain-barré syndrome-associated Campylobacter jejuni strains by human macrophages
Infection and Immunity , Volume 81 - Issue 6 p. 2095- 2103
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 GBSassociated 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 GM1aand GD1a-like epitopes, bind to hSn. This observation is of importance, as these epitopes are frequently the targets of the crossreactive 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 monocytederived 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.
|Infection and Immunity|
|Organisation||Department of Pediatrics|
Heikema, A.P, Koning, R.I, Rico, S.D.S, Rempel, H, Jacobs, B.C, Endtz, H.P, … Samsom, J.N. (2013). Enhanced, sialoadhesin-dependent uptake of guillain-barré syndrome-associated Campylobacter jejuni strains by human macrophages. Infection and Immunity, 81(6), 2095–2103. doi:10.1128/IAI.01437-12