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Human CD14dim Monocytes Patrol and Sense Nucleic Acids and Viruses via TLR7 and TLR8 Receptors
CD14dim monocytes were weak phagocytes and did not produce ROS or cytokines in response to cell-surface Toll-like receptors, but selectively produced TNF-α, IL-1β, and CCL3 inresponse to viruses and immune complexes containing nucleic acids, via a proinflammatory TLR7-TLR 8-MyD88-MEK pathway. Expand
TLR3 Deficiency in Patients with Herpes Simplex Encephalitis
Human TLR3 appears to be redundant in host defense to most microbes but is vital for natural immunity to HSV-1 in the CNS, which suggests that neurotropic viruses have contributed to the evolutionary maintenance ofTLR3. Expand
Herpes Simplex Virus Encephalitis in Human UNC-93B Deficiency
A genetic etiology for HSE is elucidated in two children with autosomal recessive deficiency in the intracellular protein UNC-93B, resulting in impaired cellular interferon-α/β and -λ antiviral responses. Expand
Autoantibodies against type I IFNs in patients with life-threatening COVID-19
A means by which individuals at highest risk of life-threatening COVID-19 can be identified is identified, and the hypothesis that neutralizing auto-Abs against type I IFNs may underlie critical CO VID-19 is tested. Expand
Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
The COVID Human Genetic Effort established to test the general hypothesis that life-threatening COVID-19 in some or most patients may be caused by monogenic inborn errors of immunity to SARS-CoV-2 with incomplete or complete penetrance finds an enrichment in variants predicted to be loss-of-function (pLOF), with a minor allele frequency <0.001. Expand
Selective predisposition to bacterial infections in IRAK-4–deficient children: IRAK-4–dependent TLRs are otherwise redundant in protective immunity
The IRAK-4–dependent TLRs and IL-1Rs are therefore vital for childhood immunity to pyogenic bacteria, particularly Streptococcus pneumoniae, and appear to play a redundant role in protective immunity to most infections. Expand
Heterozygous TBK1 mutations impair TLR3 immunity and underlie herpes simplex encephalitis of childhood
Two unrelated children with HSE carry distinct heterozygous mutations in the gene encoding TANK-binding kinase 1, which results in atypical prognosis for both parents. Expand
Human Toll‐like receptor‐dependent induction of interferons in protective immunity to viruses
Summary: Five of the 10 human Toll‐like receptors (TLRs) (TLR3, TLR4, TLR7, TLR8, and TLR9), and four of the 12 mouse TLRs (TLR3, TLR4, TLR7, TLR9) can trigger interferon (IFN)‐α, IFN‐β, and IFN‐λ,Expand
Inborn errors of interferon (IFN)‐mediated immunity in humans: insights into the respective roles of IFN‐α/β, IFN‐γ, and IFN‐λ in host defense
These experiments of nature suggest that the three types of IFNs play at least two different roles in host defense, whereas IFN‐γ is essential for anti‐mycobacterial immunity, whereasIFN‐α/β and IFn‐λ are essential forAnti‐viral immunity. Expand
The human gene damage index as a gene-level approach to prioritizing exome variants
The gene damage index (GDI) is described, a genome-wide, gene-level metric of the mutational damage that has accumulated in the general population, and it is found that the GDI was correlated with selective evolutionary pressure, protein complexity, coding sequence length, and the number of paralogs. Expand