Extracellular ATP and related nucleotides promote a wide range of pathophysiological responses via activation of cell surface purinergic P2 receptors. Almost every cell type expresses P2 receptors and/or exhibit regulated release of ATP. In this review, we focus on the purinergic receptor distribution in inflammatory cells and their implication in diverse immune responses by providing an overview of the current knowledge in the literature related to purinergic signaling in neutrophils, macrophages, dendritic cells, lymphocytes, eosinophils, and mast cells. The pathophysiological role of purinergic signaling in these cells include among others calcium mobilization, actin polymerization, chemotaxis, release of mediators, cell maturation, cytotoxicity, and cell death. We finally discuss the therapeutic potential of P2 receptor subtype selective drugs in inflammatory conditions.

This report demonstrates SOL IL-5Ralpha transcript and protein up-regulation in NP. Soluble IL-5Ralpha differentiates nasal polyps with or without concomitant asthma. As SOL IL-5Ralpha is strongly up-regulated for disease and has antagonistic properties in vitro, our studies shed new light on the mechanisms of specific immunomodulatory therapies, such as anti-IL-5.

Background Herbal remedies of Echinacea purpurea tinctures are widely used today to reduce common cold respiratory tract infections. Methods Transcriptome, epigenome and kinome profiling allowed a systems biology level characterisation of genomewide immunomodulatory effects of a standardized Echinacea purpurea (L.) Moench extract in THP1 monocytes. Results Gene expression and DNA methylation analysis revealed that Echinaforce® treatment triggers antiviral innate immunity pathways, involving tonic IFN signaling, activation of pattern recognition receptors, chemotaxis and immunometabolism. Furthermore, phosphopeptide based kinome activity profiling and pharmacological inhibitor experiments with filgotinib confirm a key role for Janus Kinase (JAK)-1 dependent gene expression changes in innate immune signaling. Finally, Echinaforce® treatment induces DNA hypermethylation at intergenic CpG, long/short interspersed nuclear DNA repeat elements (LINE, SINE) or long termininal DNA repeats (LTR). This changes transcription of flanking endogenous retroviral sequences (HERVs), involved in an evolutionary conserved (epi) genomic protective response against viral infections. Conclusions Altogether, our results suggest that Echinaforce® phytochemicals strengthen antiviral innate immunity through tonic IFN regulation of pattern recognition and chemokine gene expression and DNA repeat hypermethylated silencing of HERVs in monocytes. These results suggest that immunomodulation by Echinaforce® treatment holds promise to reduce symptoms and duration of infection episodes of common cold corona viruses (CoV), Severe Acute Respiratory Syndrome (SARS)-CoV, and new occurring strains such as SARS-CoV-2, with strongly impaired interferon (IFN) response and weak innate antiviral defense.

Human papillomavirus (HPV) infection is the prime elicitor of cervical and head-and-neck cancers. The HPV genome enters the nucleus during mitosis when the nuclear envelope dismantles. Since lamins safeguard nuclear integrity during interphase, we asked to what extent their loss would affect early HPV infection. We challenged human cervical cancer cells knocked out for the major lamin genes with a HPV16 pseudovirus (PsV) encoding an EGFP reporter and found that loss of lamin B1 amplified infection rate. A prolonged mitotic window and extensive nuclear rupture propensity during interphase led to a higher nuclear PsV load in LMNB1 knockout cells, but unchanged EGFP transcript levels pointed to an additional defect in protein turnover. We found a strong decrease in autophagic capacity in LMNB1 knockout cells, which we connect to the persistent activation of cGAS. Thus, loss of lamin B1 increases nuclear perviousness and blunts the autophagic capacity, which primes cells for unrestrained buildup of HPV capsids.

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