Human thioredoxin, a damage-associated molecular pattern and Malassezia-crossreactive autoallergen, modulates immune responses via the C-type lectin receptors Dectin-1 and Dectin-2.

Human thioredoxin (hTrx), which can be secreted from cells upon stress, functions in allergic skin inflammation as a T cell antigen due to homology and cross-reactivity with the fungal allergen Mala s13 of the skin-colonizing yeast Malassezia sympodialis. Recent studies have shown that cell wall polysaccharides of Malassezia are detected by the immune system via the C-type lectin receptors Dectin-1 and Dectin-2, which are expressed on myeloid cells. Therefore, this study aimed to investigate a putative interaction between Dectin-1, Dectin-2 and the allergens Mala s13 and hTrx. Stimulation of human monocyte-derived dendritic cells or macrophages with Mala s13 or hTrx resulted in remarkable secretion of IL-1ß and IL-23. Blocking experiments suggest that hTrx induces IL-23 by Dectin-1 binding and IL-1ß by binding to either Dectin-1 or Dectin-2. Regarding Mala s13, Dectin-1 appears to be involved in IL-1ß signaling. Interference of Syk kinase function was performed to investigate downstream signaling, which led to diminished hTrx responses. In our experiments, we observed rapid internalization of Mala s13 and hTrx upon cell contact and we were able to confirm direct interaction with Dectin-1 as well as Dectin-2 applying a fusion protein screening platform. We hypothesize that this cytokine response may result in a Th2/Th17-polarizing milieu, which may play a key role during the allergic sensitization in the skin, where allergen presentation to T cells is accompanied by microbial colonization and skin inflammation.

Vaccination of calves with yeast- and bacterial-expressed paramyosin from the bovine lungworm Dictyocaulus viviparus.

Previously, vaccination of cattle with Escherichia coli-expressed bovine lungworm paramyosin (EcPMY) adjuvanted with Quil A resulted in considerable reduction in worm burden and larvae shedding (Strube et al., 2015). To further evaluate the protective potential of PMY, cattle vaccination trials were performed using either E. coli- (EcPMY) or Pichia pastoris-expressed PMY (PpPMY) with different adjuvants (Matrix-Q(™) or Quil A). Combinations EcPMY+Matrix-Q(™) (trial 1), PpPMY+Matrix-Q(™) (trial 2) and PpPMY+Quil A (trial 3) were tested against challenge infections with 2000 Dictyocaulus viviparus larvae. Even though GM worm burden and larvae shedding was lower in almost all vaccinated groups, there were high variations between individuals hampering significant differences. However, in all vaccinated groups, lungworms were significantly shorter compared with those in controls. In vitro stimulation of peripheral blood mononuclear cells (PBMC) with recombinant (r)PMY revealed no significant proliferation following vaccinations or challenge infection. All vaccinated cattle showed a significant rise in specific antibodies, particularly IgG and its subclass IgG1, and detected the native lungworm PMY in immunoblots starting 2 weeks after the first vaccination. The use of a different rPMY-adjuvant combination or combined vaccination with additional recombinant antigens might be a promising future approach towards a new vaccine against lungworms in cattle.