Autor(es): Heikema Astrid P,Bergman Mathijs P,Richards Hannah,Crocker Paul R,Gilbert Michel,Samsom Janneke N,van Wamel Willem J B,Endtz Hubert P,van Belkum Alex

Resumo: In Campylobacter jejuni-induced Guillain-Barré syndrome (GBS), molecular mimicry between C. jejuni lipooligosaccharide (LOS) and host gangliosides leads to the production of cross-reactive antibodies directed against the peripheral nerves of the host. Currently, the presence of surface exposed sialylated LOS in C. jejuni is the single known bacterial pathogenesis factor associated with the development of GBS. Using a unique, well-characterized strain collection, we demonstrate that GBS-associated C. jejuni strains bind preferentially to sialoadhesin (Sn, Siglec-1, or CD169), a sialic acid receptor found on a subset of macrophages. In addition, using a whole-cell enzyme-linked immunosorbent assay (ELISA), C. jejuni strains with sialylated LOS bound exclusively to soluble Sn. Mass spectrometry revealed that binding was sialic acid-linkage specific with a preference for alpha(2,3)-linked sialic acid attached to the terminal galactose of the LOS chain as seen in the gangliosides GD1a, GM1b, and GM3. This molecular interaction was also related to functional consequences as a GBS-associated C. jejuni strain that bound Sn in a whole-cell ELISA adhered to surface-expressed Sn of Sn-transfected CHO cells but was unable to adhere to wild-type CHO cells. Moreover, a sialic acid-negative mutant of the same C. jejuni strain was unable to bind Sn-transfected CHO cells. This is the first report of the preferential binding of GBS-associated C. jejuni strains to the Sn immune receptor (P = 0.014). Moreover, because this binding is dependent on sialylated LOS, the main pathogenic factor in GBS progression, the present findings bring us closer to unraveling the mechanisms that lead to formation of cross-reactive antibodies in GBS disease.

Imprenta: Infection and Immunity, v. 78, n. 7, p. 3237-3246, 2010

Identificador do objeto digital: 10.1128/IAI.01273-09

Descritores: Guillain-Barre Syndrome - Biosynthesis ; Guillain-Barre Syndrome - Cell ; Guillain-Barre Syndrome - Pathogenesis ; Guillain-Barre Syndrome - Proteins ; Guillain-Barre Syndrome - Antibodies ; Guillain-Barre Syndrome - Infectious diseases

Data de publicação: 2010

INDICADORES

ACESSO