TLR7 and TLR8 activate distinct pathways in monocytes during RNA virus infection

Human blood CD14+ monocytes are bone marrow–derived white blood cells that sense and respond to pathogens. Although innate immune activation by RNA viruses preferentially occurs through intracellular RIG-I–like receptors, other nucleic acid recognition receptors, such as Toll-like receptors (TLRs), play a role in finely programming the final outcome of virus infection. Here, we dissected how human monocytes respond to infection with either Coxsackie (CV), encephalomyocarditis (EMCV), influenza A (IAV), measles (MV), Sendai (SV), or vesicular stomatitis (VSV) virus. We found that in monocytes, type I interferon (IFN) and cytokine responses to infection were RNA virus specific and differentially involved TLR7 and TLR8, which sense single-stranded RNA. These TLRs activated distinct signaling cascades in monocytes, which correlated with differences in the production of cytokines involved in the polarization of CD4+ T helper cells. Furthermore, we found that TLR7 signaling specifically increased expression of the transcription factor FOSL1, which reduced IL-27 and TNFα production by monocytes. TLR7, but not TLR8, activation of monocytes also stimulated Ca2+ flux that prevented type I IFN responses. Our work demonstrates that in human monocytes, TLR7 and TLR8 triggered different signaling pathways that contribute to distinct phenotypes during RNA virus infection. In addition, we defined individual targets within these pathways that promoted specific T helper and a...
Source: Signal Transduction Knowledge Environment - Category: Science Authors: Tags: STKE Research Articles Source Type: news

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Purpose of review Studying primary immunodeficiencies (PIDs) provides insights into human antiviral immunity in the natural infectious environment. This review describes new PIDs with genetic defects that impair innate antiviral responses. Recent findings New genetic defects in the interferon (IFN) signaling pathway include IFNAR1 deficiency, which causes uncontrolled infections with measles-mumps-rubella or yellow fever vaccines, and possibly also cytomegalovirus (CMV); and IRF9 deficiency, which results in influenza virus susceptibility. Genetic defects in several pattern recognition receptors include MDA5 deficienc...
Source: Current Opinion in Pediatrics - Category: Pediatrics Tags: ALLERGY, IMMUNOLOGY AND RELATED DISORDERS: Edited by Jordan S. Orange Source Type: research
Abstract Human blood CD14+ monocytes are bone marrow-derived white blood cells that sense and respond to pathogens. Although innate immune activation by RNA viruses preferentially occurs through intracellular RIG-I-like receptors, other nucleic acid recognition receptors, such as Toll-like receptors (TLRs), play a role in finely programming the final outcome of virus infection. Here, we dissected how human monocytes respond to infection with either Coxsackie (CV), encephalomyocarditis (EMCV), influenza A (IAV), measles (MV), Sendai (SV), or vesicular stomatitis (VSV) virus. We found that in monocytes, type I inter...
Source: Science Signaling - Category: Biomedical Science Authors: Tags: Sci Signal Source Type: research
This study was conducted to enhance the rate of advance care planning conversations and documentation by improving knowledge, attitudes, and skills of caregivers.      Read more   Violence and Trauma ...
Source: Johns Hopkins University and Health Systems Archive - Category: Nursing Source Type: news
Abstract The Advisory Committee on Immunization Practices (ACIP) recommends that children be vaccinated against 14 potentially serious illnesses during the first 24 months of life (1). CDC used data from the National Immunization Survey-Child (NIS-Child) to assess vaccination coverage with the recommended number of doses of each vaccine at the national, state, territorial, and selected local levels* among children born in 2015 and 2016. Coverage by age 24 months was at least 90% nationally for ≥3 doses of poliovirus vaccine, ≥1 dose of measles, mumps, and rubella vaccine (MMR), ≥3 doses of hepatitis B vac...
Source: MMWR Morb Mortal Wkl... - Category: Epidemiology Authors: Tags: MMWR Morb Mortal Wkly Rep Source Type: research
In conclusion, European countries now have more comprehensive national vaccination programs for HCP, however there are still gaps. Given the recent large outbreaks of vaccine-preventable diseases in Europe and the occupational risk for HCP, vaccination policies need to be expanded and strengthened in several European countries. Overall, vaccination policies for HCP in Europe should be periodically re-evaluated in order to provide optimal protection against vaccine-preventable diseases and infection control within healthcare facilities for HCP and patients. PMID: 31623916 [PubMed - as supplied by publisher]
Source: Vaccine - Category: Allergy & Immunology Authors: Tags: Vaccine Source Type: research
Carter Roberts’ motorized wheelchair didn’t arrive until the day he died. It had been a long time coming and his parents had fought hard to get it. The chair cost more than $32,000 and the insurance companies wouldn’t cover it, so the family went to court. One insurer eventually agreed to pay for some components of the chair but not the whole thing. And then none of it mattered anyway. On Sept. 22, 2018, the Roberts’ doorbell rang and the chair was delivered. Also on Sept. 22, 2018, Carter died, just three months shy of his sixth birthday. He had been largely paralyzed for the final two years of his...
Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized Infectious Disease viruses Source Type: news
Sanofi Pasteur says some surgeries may face supply delays of up to two weeks Related items fromOnMedica Measles cases triple in Europe but immunisation rates grow Doctors promise 'flu vaccine is on its way' Decision to give boys HPV jab will save thousands of lives BMJ report questions swine flu jab transparency Doctors to offer newly licensed flu vaccine
Source: OnMedica Latest News - Category: UK Health Source Type: news
Conclusions These data indicate that JCV-specific antibodies are produced intrathecally in a minority of patients with MS, and NAT treatment affects the intrathecal humoral immune response against JCV relatively specifically compared with other neurotropic viruses. Further studies are needed to determine whether this effect translates to higher risk of progressive multifocal leukoencephalopathy development.
Source: Neurology Neuroimmunology and Neuroinflammation - Category: Neurology Authors: Tags: Cerebrospinal Fluid, Multiple sclerosis Article Source Type: research
Conclusion: Uganda successfully developed a national multi-hazard emergency preparedness and response plan using the preparedness logic model. The plan is now ready for implementation by the Uganda MoH and partners. PMID: 31526179 [PubMed - in process]
Source: Global Health Action - Category: International Medicine & Public Health Tags: Glob Health Action Source Type: research
Abstract It remains uncertain why most infectious disease mortalities disappeared before modern medical interventions. Historical epidemiology using prospectively collected U.S. Army data from the Civil War (1860-1861), Spanish-American War (1898-1899), and First World War (1917-1918) suggests that epidemiological isolation was a major mortality risk factor for soldiers. Morbidity and mortality due to common infections decreased progressively from 1860 to 1918, except for influenza during the 1918 pandemic. Adult measles or mumps infections are indicative of isolated rural populations and correlated with disease m...
Source: The American Journal of Tropical Medicine and Hygiene - Category: Tropical Medicine Authors: Tags: Am J Trop Med Hyg Source Type: research
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