Hot-water soluble polysaccharides H-1-3 and H-2-1 were isolated from the thalli of the lichen Xanthoria parietina (L.) Th. Fr. and purified by ion exchange and gel permeation chromatography. Structure elucidation was mainly based on 2D-NMR and nano-ESI-Q-TOF MS/MS experiments. H-1-3 (13.7?kDa) was shown to be linear α-glucan with α-d-Glcp-(1?→?[→[4)-α-d-Glcp-(1]2?→?[6)-α-d-Glcp-(1]3?→?4)]n core backbone. The (1,4)- and (1,6)-α-d-Glcp linkages were in a 2:3?M ratio. H-2-1 (525?kDa) was characterized as a complex branched β-galacto-α-mannan with →[6)-α-d-Manp-(1?→?[2,6)-α-d-Manp-(1]2?→?[2)-α-d-Manp-(1]2→]n core units and main side chains of (1,3)-β-d-Galf linked at O-6 to →2)-α-d-Manp-(1→, together with minor terminal units of 1,4/1,6-α-D -Glcp units attached to the core chain at O-6 position and α-L-Rhap linked to Galf side chain at O-2 position (Manp: Galf: Glcp: Rhap linkage ratio?=?9:3:2:1). H-2-1 exerted strong immunoactivity in vitro and activated murine RAW macrophages 264.7 towards significantly increased phagocytosis, TNF-α and IL-1β secretion. These effects are due to an interaction of the galactomannan with the transmembrane pattern-recognition protein Dectin-2 of the macrophages.,Copyright ? 2019 Elsevier B.V. All rights reserved.