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<p>Toll-like receptor (TLR)-10 remains an orphan receptor without well-characterized ligands or functions. Here, we reveal that TLR10 is predominantly localized to endosomes and binds dsRNA in vitro at endosomal pH, suggesting that dsRNA is a ligand of TLR10. Recognition of dsRNA by TLR10 activates recruitment of myeloid differentiation primary response gene 88 for signal transduction and suppression of interferon regulatory factor-7 dependent type I IFN production. We also demonstrate crosstalk between TLR10 and TLR3, as they compete with each other for dsRNA binding. Our results suggest for the first time that dsRNA is a ligand for TLR10 and propose novel dual functions of TLR10 in regulating IFN signaling: first, recognition of dsRNA as a nucleotide-sensing receptor and second, sequestration of dsRNA from TLR3 to inhibit TLR3 signaling in response to dsRNA stimulation.</p

Meteorological conditions and air pollution concentrations in 1998

<p>Meteorological conditions and air pollution concentrations in 1998</p

Descriptive statistics of all adults who died at age 30 or above in year 1998

<p>E₀ = never/seldom; E₁ = low/moderate; E₂ = frequent</p

Plots of weekly proportion of total specimens positive for influenza isolation in 1998.

<p>Plots of weekly proportion of total specimens positive for influenza isolation in 1998.</p

Excess risk (ER) % in the never/seldom exercise group, and difference in excess risk (ΔER)% of mortality associated with each 10% increase in influenza intensity for low/moderate and frequent exercise relative to the never/seldom exercise.

<p>ER% were assessed by Poisson regression, and ΔER% were assessed by multinomial logistic regression, negative values indicate odds reduction vs never/seldom exercise (P-values: ^*<0.05 ^**<0.01 ^***<0.001 ^****<0.0001); ‘Never/Seldom’ means adults who never exercised or exercised less than once per month, ‘Low/Moderate’ means adults who exercised at least once per month to three times per week, and ‘Frequent’ means adults who exercised four times or more per week</p

Antigenic characterization of Indian clade 2.3.2 H5N1 viruses.

<p>*- reciprocal of antibody titres by hemagglutination inhibition test.</p

Circulation of H5N1 viruses in South Asia since 2010.

<p>Circulation of H5N1 viruses in South Asia since 2010.</p

Circulation of H5N1 viruses in South Asia till 2009.

<p>Circulation of H5N1 viruses in South Asia till 2009.</p

Phylogenetic relationships of the coding sequences of hemagglutinin (HA) genes of representative influenza A viruses.

<p>Analysis was based on full length or near full length sequences. The numbers next to the branch nodes indicate bootstrap values/posterior probabilities expressed as percentages from, respectively, 500 bootstrap replicates of a maximum likelihood tree and posterior probabilities from a MrBayes 3.2 analysis (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031844#s3" target="_blank">methods</a>). Not all support valuess are shown due to space constraints. Numbers labeled on the HA tree refer to the WHO H5N1 clade designations (<a href="http://www.who.int/csr/disease/avian_influenza/guidelines/nomenclature/en" target="_blank">http://www.who.int/csr/disease/avian_influenza/guidelines/nomenclature/en</a>). Viruses isolated in this work are in green and other recent Indian, Bangladesh and Bhutan viruses are in red. Scale bar, indicates nucleotide substitutions per site.</p

Phylogenetic relationships of polymerase acidic (PA) genes of representative influenza A viruses.

<p>Details are as in the legends to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031844#pone-0031844-g001" target="_blank">Figures 1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031844#pone-0031844-g002" target="_blank">2</a>.</p