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

Related Links:

Some directly transmitted human pathogens, such as influenza and measles, generate sustained exponential growth in incidence and have a high peak incidence consistent with the rapid depletion of susceptible individuals. Many do not. While a prolonged exponential phase typically arises in traditional disease-dynamic models, current quantitative descriptions of nonstandard epidemic...
Source: Proceedings of the National Academy of Sciences - Category: Science Authors: Tags: Biological Sciences Source Type: research
In this study, we aimed to decode molecular signatures and pathways of the host cells in response to SARS-CoV-2 and the rapid identification of repurposable drugs using bioinformatics and network biology strategies. We have analyzed available transcriptomic RNA-seq COVID-19 data to identify differentially expressed genes (DEGs). We detected 177 DEGs specific for COVID-19 where 122 were upregulated and 55 were downregulated compared to control (FDR
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research
(American Chemical Society) Vaccines have curtailed the spread of several infectious diseases, such as smallpox, polio and measles. However, vaccines against some diseases, including HIV-1, influenza and malaria, don't work very well, and one reason could be the timing of antigen and adjuvant presentation to the immune system. Now, researchers reporting inACS Central Science developed an injectable hydrogel that allows sustained release of vaccine components, increasing the potency, quality and duration of immune responses in mice.
Source: EurekAlert! - Infectious and Emerging Diseases - Category: Infectious Diseases Source Type: news
While the world waits for a COVID-19 vaccine, children across the globe are going without shots already known to be life-saving. With the world in disarray due to the COVID-19 pandemic, the number of children vaccinated this year against infections like diphtheria, tetanus, pertussis, measles and pneumococcal disease has fallen to levels not seen since the 1990s, according to a new report from the Bill and Melinda Gates Foundation. “In other words,” the report reads, “we’ve been set back about 25 years in about 25 weeks.” That stark figure comes from the Gates Foundation’s annual Goalkee...
Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized COVID-19 Source Type: news
CONCLUSIONS: The USMA experience mirrored what was occurring in the larger U.S. Army in the early 20th century and may serve as a model for the application of NPIs in response to modern infectious diseases resulting from novel or unknown etiologies. PMID: 32870979 [PubMed - as supplied by publisher]
Source: Military Medicine - Category: International Medicine & Public Health Tags: Mil Med Source Type: research
In this study, the antiviral effect of favipiravir against measles virus (Edmonston strain) and SSPE virus (Yamagata-1 strain) was examined in vitro. The 50% effective concentrations of favipiravir (inhibiting viral plaque formation by 50%) for Edmonston and Yamagata-1 strains were 108.7 ± 2.0 μM (17.1 ± 0.3 μg/mL) and 38.6 ± 6.0 μM (6.1 ± 0.9 μg/mL), respectively, which were similar to those of ribavirin. The antiviral activity of favipiravir against the SSPE virus was demonstrated, for the first time, in this study. PMID: 32863356 [PubMed - as supplied by publisher]
Source: Japanese Journal of Infectious Diseases - Category: Infectious Diseases Authors: Tags: Jpn J Infect Dis Source Type: research
Many months into the COVID-19 pandemic, the coronavirus is still spreading uncontrolled through the U.S. Public health authorities including the U.S. Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) tell us to remain six feet apart, wash our hands, disinfect frequently touched surfaces, and wear masks. But compliance with these measures—especially masks—is mixed, and daily we hear of cases where people do not know how they were infected. We hear about superspreading events, where one person infects many, happening in crowded bars and family gatherings, but not at outdoor ...
Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized COVID-19 Source Type: news
Abstract BACKGROUND: Denmark has no general recommendations for vaccination of healthcare workers (HCWs). We explored the self-reported immunity to varicella, measles, mumps, and rubella, reasons for receiving the influenza vaccine or not, and opinions on vaccination of HCWs against varicella, MMR, pertussis, diphtheria, and influenza among staff from departments with a high risk of exposure to infectious agents. METHODS: From May 2019 to August 2019, a structured questionnaire was distributed to clinical and non-clinical HCWs at a tertiary and a general paediatric department in Denmark. Self-reported immunit...
Source: Vaccine - Category: Allergy & Immunology Authors: Tags: Vaccine Source Type: research
Conclusions and Implications of Key FindingsThe review yielded 37 articles and 267 sets of cost estimates. We found no cost-of-illness studies with cost estimates for hepatitis B, measles, rubella, or yellow fever from primary data. Most estimates were from countries in Gavi preparatory (28%) and accelerated (28%) transition, followed by those who are initiating self-financing (22%) and those not eligible for Gavi support (19%). Thirteen articles compared household expenses to manage illnesses with income and two articles with other household expenses, such as food, clothing, and rent. An episode of illness represented 1 &...
Source: PharmacoEconomics - Category: Health Management Source Type: research
By MICHEL ACCAD, MD With cases of COVID-19 either disappeared or rapidly diminishing from places like Wuhan, Italy, New York, and Sweden, many voices are speculating that herd immunity may have been reached in those areas and that it may be at hand in the remaining parts of the world that are still struggling with the pandemic.  Lockdowns should end—or may not have been needed to begin with, they conclude. Adding plausibility to their speculation is the discovery of biological evidence suggesting that prior exposure to other coronaviruses may confer some degree of immunity against SARS-CoV...
Source: The Health Care Blog - Category: Consumer Health News Authors: Tags: COVID-19 Health Policy immunity MICHEL ACCAD Pandemic Source Type: blogs
More News: Environmental Health | Influenza | Measles | Science