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A study of the cross-reactivity among somatic and excretory-secretory antigens of the third stage larvae of Anisakis simplex s.l. and somatic antigens of other ascarid nematodes (Ascaris lumbricoides, A. suum, Toxocara canis, Anisakis physeteris, Hysterothylacium aduncum and H. fabri) was carried out by immunoblotting. It was revealed a high degree of cross-reactivity among ascarids in the 30 and> 212 kDa range by using sera against somatic and excretory-secretory antigens of A. simplex s.l. It has been revealed also specific components of the Anisakis genus (< 7.2, 9, 19 and 25 kDa) that will be interesting in diagnosis.

BackgroundVirus infections drive COPD exacerbations and progression. Anti-viral immunity centers on the activation of virus-specific CD8+T cells by viral epitopes presented on MHC class I molecules of infected cells. These epitopes are generated by the immunoproteasome, a specialized intracellular protein degradation machine, which is induced by anti-viral cytokines in infected cells.MethodsWe here analysed the effects of CS on cytokine and virus-mediated induction of the immunoproteasomein vitro,ex vivoandin vivousing RNA and Western blot analyses. CD8+T cell activation was determined in co-culture assays with CS-exposed Influenza A virus (IAV)-infected cells. Mass-spectrometry-based analysis of MHC class I-bound peptides uncovered the effects of CS on inflammatory antigen presentation in lung cells. IAV-specific CD8+T cell numbers were determined in peripheral patients’ blood using tetramer-technology.ResultsCS impaired the induction of the immunoproteasome by cytokine signaling and viral infection in lung cellsin vitro,ex vivoandin vivo. CS also altered the peptide repertoire of antigens presented on MHC class I under inflammatory conditions. Importantly, MHC class I-mediated activation of IAV-specific CD8+T cells was dampened by CS. COPD patients exhibited reduced numbers of circulating IAV-specific CD8+T cells compared to healthy controls and asthmatics.ConclusionOur data indicate that cigarette smoke interferes with MHC class I antigen generation and presentation and thereby contributes to impaired activation of CD8+T cells upon virus infection. This adds important mechanistic insight on how cigarette smoke mediates increased susceptibility of smokers and COPD patients to viral infections.

Type II alveolar epithelial cell (AECII) redox imbalance contributes to the pathogenesis of idiopathic pulmonary fibrosis (IPF) -a deadly disease with restricted and limited treatment options. Here, we show that expression of membrane-bound cytochrome B5 reductase 3 (CYB5R3), an enzyme critical for maintaining cellular redox homeostasis and soluble guanylate cyclase (sGC) heme iron redox state, is diminished in IPF AECII. Deficiency of CYB5R3 in AECII leads to sustained activation of the profibrotic factor TGF-β1 and increased susceptibility to lung fibrosis. We further show that CYB5R3 is a critical regulator of ERK1/2 phosphorylation and sGC-cGMP-protein kinase G axis that modulates activation of TGF-β1 signaling pathway. We demonstrate that sGC agonists are effective in reducing the pulmonary fibrotic outcomes of in vivo deficiency of CYB5R3 in AECII. Taken together, these results establish that CYB5R3 in AECII is required to maintain resilience against lung injury and fibrosis, and that therapeutic manipulation of sGC redox state could provide a basis for treating fibrotic conditions in the lung and beyond.

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