Campylobacter jejuni lipooligosaccharides modulate dendritic cell-mediated T cell polarization in a sialic acid linkage-dependent manner.
Autor(es): Bax Marieke,Kuijf Mark L,Heikema Astrid P,van Rijs Wouter,Bruijns Sven C M,García-Vallejo Juan J,Crocker Paul R,Jacobs Bart C,van Vliet Sandra J,van Kooyk Yvette
Resumo: Carbohydrate mimicry between Campylobacter jejuni lipooligosaccharides (LOS) and host neural gangliosides plays a crucial role in the pathogenesis of Guillain-Barré syndrome (GBS). Campylobacter jejuni LOS may mimic various gangliosides, which affects the immunogenicity and the type of neurological deficits in GBS patients. Previous studies have shown the interaction of LOS with sialic acid-specific siglec receptors, although the functional consequences remain unknown. Cells that express high levels of siglecs include dendritic cells (DCs), which are crucial for initiation and differentiation of immune responses. We confirm that ?2,3-sialylated GD1a/GM1a mimic and ?2,8-sialylated GD1c mimic LOS structures interact with recombinant Sn and siglec-7, respectively. Although the linkage of the terminal sialic acid of LOS did not regulate expression of DC maturation markers, it displayed clear opposite expression levels of interleukin-12 (IL-12) and OX40L, molecules involved in DC-mediated Th cell differentiation. Accordingly, targeting DC-expressed siglec-7 with ?2,8-linked sialylated LOS resulted in Th1 responses, whereas Th2 responses were induced by targeting with LOS containing ?2,3-linked sialic acid. Thus, our data demonstrate for the first time that depending on the sialylated composition of Campylobacter jejuni LOS, specific Th differentiation programs are initiated, possibly through targeting of distinct DC-expressed siglecs.
Imprenta: Infection and Immunity, v. 79, n. 7, p. 2681-2689, 2011
Identificador do objeto digital: 10.1128/IAI.00009-11
Descritores: Guillain-Barre Syndrome - Biosynthesis ; Guillain-Barre Syndrome - Cell ; Guillain-Barre Syndrome - Molecular Structure ; Guillain-Barre Syndrome - Pathogenesis ; Guillain-Barre Syndrome - Proteins ; Guillain-Barre Syndrome - Cytokines ; Guillain-Barre Syndrome - Immunology
Data de publicação: 2011