Role of deficits in pathogen recognition receptors in infection susceptibility

This work was supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013), and the Fundação para a Ciência e Tecnologia (FCT) (IF/00735/2014 to A.C. and SFRH/BPD/96176/2013 to C.C.

Plant and Animal Pathogen Recognition Receptors Signal through Non-RD Kinases

Plants and animals mediate early steps of the innate immune response through pathogen recognition receptors (PRRs). PRRs commonly associate with or contain members of a monophyletic group of kinases called the interleukin-1 receptor-associated kinase (IRAK) family that include Drosophila Pelle, human IRAKs, rice XA21 and Arabidopsis FLS2. In mammals, PRRs can also associate with members of the receptor-interacting protein (RIP) kinase family, distant relatives to the IRAK family. Some IRAK and RIP family kinases fall into a small functional class of kinases termed non-RD, many of which do not autophosphorylate the activation loop. We surveyed the yeast, fly, worm, human, Arabidopsis, and rice kinomes (3,723 kinases) and found that despite the small number of non-RD kinases in these genomes (9%–29%), 12 of 15 kinases known or predicted to function in PRR signaling fall into the non-RD class. These data indicate that kinases associated with PRRs can largely be predicted by the lack of a single conserved residue and reveal new potential plant PRR subfamilies

Pathogen Recognition Receptor Signaling Accelerates Phosphorylation-Dependent Degradation of IFNAR1

An ability to sense pathogens by a number of specialized cell types including the dendritic cells plays a central role in host's defenses. Activation of these cells through the stimulation of the pathogen-recognition receptors induces the production of a number of cytokines including Type I interferons (IFNs) that mediate the diverse mechanisms of innate immunity. Type I IFNs interact with the Type I IFN receptor, composed of IFNAR1 and IFNAR2 chains, to mount the host defense responses. However, at the same time, Type I IFNs elicit potent anti-proliferative and pro-apoptotic effects that could be detrimental for IFN-producing cells. Here, we report that the activation of p38 kinase in response to pathogen-recognition receptors stimulation results in a series of phosphorylation events within the IFNAR1 chain of the Type I IFN receptor. This phosphorylation promotes IFNAR1 ubiquitination and accelerates the proteolytic turnover of this receptor leading to an attenuation of Type I IFN signaling and the protection of activated dendritic cells from the cytotoxic effects of autocrine or paracrine Type I IFN. In this paper we discuss a potential role of this mechanism in regulating the processes of innate immunity

The microbial zoo in the C. elegans intestine: Bacteria, fungi and viruses

Press freedom has become one of the major challenges facing Journalism practice in the world. This paper explores the factors hindering press freedom in Nigeria using some relevant examples. The researcher used the qualitative method of research; using secondary data comprising of books and journals. The study is embedded on social responsibility theory. The study reveals that there are a lot of factors in Nigeria that hinders press freedom ranging from secrecy, legal pressure, direct censorship and force among others. Findings also reveal that Nigerian press freedom is a paradox and only exist on paper i.e. in the constitution but not in practice. The study recommends that since press freedom is granted in the constitution of Nigeria, there should be statutory backup and in order not to hinder press freedom, journalist should be allowed to have access to government sources and records so long as it will not bring chaos to the society at large

Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen recognition receptors

Aging leads to dysregulation of multiple components of the immune system that results in increased susceptibility to infections and poor response to vaccines in the aging population. The dysfunctions of adaptive B and T cells are well documented, but the effect of aging on innate immunity remains incompletely understood. Using a heterogeneous population of peripheral blood mononuclear cells (PBMCs), we first undertook transcriptional profiling and found that PBMCs isolated from old individuals (≥ 65 years) exhibited a delayed and altered response to stimulation with TLR4, TLR7/8, and RIG-I agonists compared to cells obtained from adults (≤ 40 years). This delayed response to innate immune agonists resulted in the reduced production of pro-inflammatory and antiviral cytokines and chemokines including TNFα, IL-6, IL-1β, IFNα, IFNγ, CCL2, and CCL7. While the major monocyte and dendritic cell subsets did not change numerically with aging, activation of specific cell types was altered. PBMCs from old subjects also had a lower frequency of CD40+ monocytes, impaired up-regulation of PD-L1 on monocytes and T cells, and increased expression of PD-L2 and B7-H4 on B cells. The defective immune response to innate agonists adversely affected adaptive immunity as TLR-stimulated PBMCs (minus CD3 T cells) from old subjects elicited significantly lower levels of adult T-cell proliferation than those from adult subjects in an allogeneic mixed lymphocyte reaction (MLR). Collectively, these age-associated changes in cytokine, chemokine and interferon production, as well as co-stimulatory protein expression could contribute to the blunted memory B- and T-cell immune responses to vaccines and infections

Podosomes of dendritic cells facilitate antigen sampling

Dendritic cells sample the environment for antigens and play an important role in establishing the link between innate and acquired immunity. Dendritic cells contain mechanosensitive adhesive structures called podosomes that consist of an actin-rich core surrounded by integrins, adaptor proteins and actin network filaments. They facilitate cell migration via localized degradation of extracellular matrix. Here, we show that podosomes of human dendritic cells locate to spots of low physical resistance in the substrate (soft spots) where they can evolve into protrusive structures. Pathogen recognition receptors locate to these protrusive structures where they can trigger localized antigen uptake, processing and presentation to activate T-cells. Our data demonstrate a novel role in antigen sampling for the podosomes of dendritic cell

Danger‐associated molecular patterns ( DAMPs ) in acute lung injury

Danger‐associated molecular patterns ( DAMPs ) are host‐derived molecules that can function to regulate the activation of pathogen recognition receptors ( PRRs ). These molecules play a critical role in modulating the lung injury response. DAMPs originate from multiple sources, including injured and dying cells, the extracellular matrix, or exist as immunomodulatory proteins within the airspace and interstitium. DAMPs can function as either toll‐like receptor ( TLR ) agonists or antagonists, and can modulate both TLR and nod‐like receptor ( NLR ) signalling cascades. Collectively, this diverse group of molecules may represent important therapeutic targets in the prevention and/or treatment of acute lung injury ( ALI ) and its more severe form, acute respiratory distress syndrome ( ARDS ).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94713/1/path4124.pd

Ligand induced cleavage and nuclear localization of the rice XA21 immune receptor

The rice XA21 receptor confers immunity to the Gram-negative bacterial pathogen, _Xanthomonas oryzae_ pv. _oryzae_ (_Xoo_) upon recognition of the conserved microbial signature AxY^S^22. Here, we demonstrate that the intracellular kinase domain of XA21 translocates to the nucleus upon AxY^S^22-mediated perception and that this translocation event is required for XA21-mediated immunity

Vitamin D and COVID-19

The ongoing COVID -19 pandemic is caused by severe acute respiratory syndrome corona virus -2 (SARS-CoV-2). Since its emergence in Wuhan in Hubei province of China in December 2019, the virus has spread to every continent except Antartica. Currently, there is no registered treatment or vaccine for the disease. In the current scenario of the deadly virus spreading across continents and the absence of a specific treatment of novel corona virus, there is an urgent need to search for alternative strategies to prevent and control the rapid replication of virus. Vitamin D supplementation may reduce the incidence, severity and risk of death from pneumonia (consequent to the cytokine storm) in the current COVID pandemic. Through its effect on innate and adaptive immunity, vitamin D can reduce the risk of viral respiratory tract infections. 1, 25(OH) vitamin D directly stimulates the production of anti-microbial peptides like defensin and Cathelicidin that can reduce the rate of viral replication. In addition, it can also reduce the concentration of pro-inflammatory cytokines that are responsible for causing cytokine storm and resultant fatal pneumonia. In order to reduce the risk of infection especially in developing country like India, it is recommended that people at risk of COVDI19 may be considered for vitamin D supplementation