Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus

Outcomes of hepatitis C virus (HCV) infection and treatment depend on viral and host genetic factors. Here we use human genome-wide genotyping arrays and new whole-genome HCV viral sequencing technologies to perform a systematic genome-to-genome study of 542 individuals who were chronically infected with HCV, predominantly genotype 3. We show that both alleles of genes encoding human leukocyte antigen molecules and genes encoding components of the interferon lambda innate immune system drive viral polymorphism. Additionally, we show that IFNL4 genotypes determine HCV viral load through a mechanism dependent on a specific amino acid residue in the HCV NS5A protein. These findings highlight the interplay between the innate immune system and the viral genome in HCV control

Ann Rheum Dis

Objective This study was conducted with sera from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and arthritis and lupus-like disease animal models to identify innate immune system-dependent and -independent autoantigens

Fresh Insights into Disease Etiology and the Role of Microbial Pathogens.

Pathogens have been implicated in the initiation and/or promotion of systemic sclerosis (scleroderma, SSc); however, no evidence was found to substantiate the direct contribution to this disease in past years. Recently, significant advances have been made in understanding the role of the innate immune system in SSc pathogenesis, supporting the idea that pathogens might interact with host innate immune-regulatory responses in SSc. In light of these findings, we review the studies that identified the presence of pathogens in SSc, along with studies on pathogens implicated in driving the innate immune dysregulation in SSc. The goal of this review is to illustrate how these pathogens, specifically viruses, may play important role both as triggers of the innate immune system, and critical players in the development of SSc disease

Interaction between Cannabinoid System and Toll-Like Receptors Controls Inflammation

Since the discovery of the endocannabinoid system consisting of cannabinoid receptors, endogenous ligands, and biosynthetic and metabolizing enzymes, interest has been renewed in investigating the promise of cannabinoids as therapeutic agents. Abundant evidence indicates that cannabinoids modulate immune responses. An inflammatory response is triggered when innate immune cells receive a danger signal provided by pathogen- or damage-associated molecular patterns engaging pattern-recognition receptors. Toll-like receptor family members are prominent pattern-recognition receptors expressed on innate immune cells. Cannabinoids suppress Toll-like receptor-mediated inflammatory responses. However, the relationship between the endocannabinoid system and innate immune system may not be one-sided. Innate immune cells express cannabinoid receptors and produce endogenous cannabinoids. Hence, innate immune cells may play a role in regulating endocannabinoid homeostasis, and, in turn, the endocannabinoid system modulates local inflammatory responses. Studies designed to probe the interaction between the innate immune system and the endocannabinoid system may identify new potential molecular targets in developing therapeutic strategies for chronic inflammatory diseases. This review discusses the endocannabinoid system and Toll-like receptor family and evaluates the interaction between them

Prion Disease and the Innate Immune System

Prion diseases or transmissible spongiform encephalopathies are a unique category of infectious protein-misfolding neurodegenerative disorders. Hypothesized to be caused by misfolding of the cellular prion protein these disorders possess an infectious quality that thrives in immune-competent hosts. While much has been discovered about the routing and critical components involved in the peripheral pathogenesis of these agents there are still many aspects to be discovered. Research into this area has been extensive as it represents a major target for therapeutic intervention within this group of diseases. The main focus of pathological damage in these diseases occurs within the central nervous system. Cells of the innate immune system have been proven to be critical players in the initial pathogenesis of prion disease, and may have a role in the pathological progression of disease. Understanding how prions interact with the host innate immune system may provide us with natural pathways and mechanisms to combat these diseases prior to their neuroinvasive stage. We present here a review of the current knowledge regarding the role of the innate immune system in prion pathogenesis

The association between 3020INSC mutation in NOD2 gene and arterial stiffness in hypertensives.

The innate immune system elicits an inflammatory process which is believed to be involved in the development of vascular damage in hypertension. The NOD2 gene (CARD15) is involved in the control of the innate immune system. The aim of this study was to assess the occurrence of the 3020insC mutation in the NOD2 gene in relation to vascular damage in hypertensives