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The induced immune response by LPS involved differential regulation of genes related to signaling and recognition, more specifically GTPases and post-translational regulation mechanisms like ubiquitination and phosphorylation. We have discovered individuality in both the immune receptor repertoire and the response to LPS, which may translate into holobiont fitness and susceptibility to stress. The three different layers of immune gene control observed in this study, – namely constitutive expression, individual-specific expression, and induced genes -, draw a complex picture of the innate immune gene regulation in H. panicea. Most likely this reflects synergistic interactions among the different components of immunity in their role to control and respond to a stable microbiome, seawater bacteria, and potential pathogens.Coronaviruses (CoVs) are a known global threat, and most recently the ongoing COVID-19 pandemic has claimed more than 2 million human lives. Delays and interference with IFN responses are closely associated with the severity of disease caused by CoV infection. As the most abundant viral protein in infected cells just after the entry step, the CoV nucleocapsid (N) protein likely plays a key role in IFN interruption. We have conducted a comprehensive comparative analysis and report herein that the N proteins of representative human and animal CoVs from four different genera [swine acute diarrhea syndrome CoV (SADS-CoV), porcine epidemic diarrhea virus (PEDV), severe acute respiratory syndrome CoV (SARS-CoV), SARS-CoV-2, Middle East respiratory syndrome CoV (MERS-CoV), infectious bronchitis virus (IBV) and porcine deltacoronavirus (PDCoV)] suppress IFN responses by multiple strategies. In particular, we found that the N protein of SADS-CoV interacted with RIG-I independent of its RNA binding activity, mediating K27-, K48- and K63-linked ubiquitination of RIG-I and its subsequent proteasome-dependent degradation, thus inhibiting the host IFN response. These data provide insight into the interaction between CoVs and host, and offer new clues for the development of therapies against these important viruses.

In mammalian species, hypoxia is a prominent feature of inflammation. The role of hypoxia in regulating macrophage responses

alteration in metabolic pathways is well established. Recently, oxidative burst-induced hypoxia has been shown in murine macrophages after phagocytosis. Despite the available detailed information on the regulation of macrophage function at transcriptomic and epigenomic levels, the association of genetic polymorphism and macrophage function has been less explored. Previously, we have shown that host genetics controls approximately 80% of the variation in an oxidative burst as measured by nitric oxide (NO

). Further studies revealed two clusters of transcription factors (hypoxia-related and inflammatory-related) are under the genetic control that shapes macrophages’ pro-inflammatory characteristics.

In the current study, the association between 43,066 autosomal Single Nucleic Polymorphism (SNPs) and the ability of MDMs in production of NO

in response to

was evaluated in 58 Hocandidate step that perhaps shapes macrophage functional characteristics in the pathway of phagocytosis leading to oxidative burst, hypoxia, cellular response to hypoxia and finally the pro-inflammatory responses. Since all cells in one individual carry the same alleles, the effect of genetic predisposition of sensitivity to hypoxia will likely be notable on the clinical outcome to a broad range of host-pathogen interactions.

The results suggest that the genetic polymorphism via regulation of response to hypoxia is a candidate step that perhaps shapes macrophage functional characteristics in the pathway of phagocytosis leading to oxidative burst, hypoxia, cellular response to hypoxia and finally the pro-inflammatory responses. Since all cells in one individual carry the same alleles, the effect of genetic predisposition of sensitivity to hypoxia will likely be notable on the clinical outcome to a broad range of host-pathogen interactions.To determine whether the neutralization activity of monoclonal antibodies, convalescent sera and vaccine-elicited sera was affected by the top five epidemic SARS-CoV-2 variants in the UK, including D614G+L18F+A222V, D614G+A222V, D614G+S477N, VOC-202012/01(B.1.1.7) and D614G+69-70del+N439K, a pseudovirus-neutralization assay was performed to evaluate the relative neutralization titers against the five SARS-CoV-2 variants and 12 single deconvolution mutants based on the variants. In this study, 18 monoclonal antibodies, 10 sera from convalescent COVID-19 patients, 10 inactivated-virus vaccine-elicited sera, 14 mRNA vaccine-elicited sera, nine RBD-immunized mouse sera, four RBD-immunized horse sera, and four spike-encoding DNA-immunized guinea pig sera were tested and analyzed. The N501Y, N439K, and S477N mutations caused immune escape from nine of 18 mAbs. However, the convalescent sera, inactivated virus vaccine-elicited sera, mRNA vaccine-elicited sera, spike DNA-elicited sera, and recombinant RBD protein-elicited sera could still neutralize these variants (within three-fold changes compared to the reference D614G variant). The neutralizing antibody responses to different types of vaccines were different, whereby the response to inactivated-virus vaccine was similar to the convalescent sera.Oral mucositis (OM) is a treatment-limiting adverse side effect of radiation and chemotherapy. Approximately 80% of patients undergoing radiotherapy (RT) for head and neck cancers (HNC) develop OM, representing a major unmet medical condition. Our understanding of the immunopathogenesis of OM is limited, due in part to the surprising paucity of information regarding healing mechanisms in the oral mucosa. RNAseq of oral tissue in a murine model that closely mimics human OM, showed elevated expression of IL-17 and related immune pathways in response to head and neck irradiation (HNI). Strikingly, mice lacking the IL-17 receptor (IL-17RA) exhibited markedly more severe OM. Restoration of the oral mucosa was compromised in Il17ra-/- mice and components associated with healing, including matrix metalloproteinase 3, 10 and IL-24 were diminished. IL-17 is typically associated with recruitment of neutrophils to mucosal sites following oral infections. RGT-018 mouse Unexpectedly, in OM the absence of IL-17RA resulted in excessive neutrophil recruitment and immunopathology.