Toll-like receptors articles from across Nature Portfolio

Interleukin-1 receptor-associated kinase 2 (IRAK2) is essential for Myddosome complex formation downstream of most Toll-like receptors. Here, the authors show a loss-of-function copy number variant of IRAK2 associated with immunodeficiency, autoimmunity, and autoinflammation, which disrupts IRAK2 interaction with IRAK4 and further downstream Myddosome formation, accompanied by enhanced interferon responses.

Paediatric acute respiratory distress syndrome (ARDS) is a potentially life-threatening condition in children, understanding the immuno-pathology is of importance. Here the authors employ a high-dimensionality approach to identify dysregulated immune pathways underpinning the condition, and find important differences compared to ARDS in adults.

Collagen based 3D tissue-like cultures have been shown to modulate HIV-1 infectivity and mode of spread. Here, the authors demonstrate that varying the density of type I collagen matrices impair HIV-1 particle fusion and sensitize virions for TLR-based innate immune recognition by macrophages implicating structural changes in Env, TLR2 interaction and TLR8 positive endosomes promoting innate immune detection of viral gRNA.

MyD88 is an immune adaptor protein that self-assembles via its TIR domain to initiate TLR and inflammatory signaling. Here, authors reveal the cryo-EM structure of MyD88 TIR filaments and show how dimerized receptors directly nucleate this assembly.

Neurotrophic factors have been shown to be involved beyond the neuronal system. Here the authors show brain derived neurotrophic factor and its derived dodecapeptide can antagonise TLR4 and can inhibit macrophage inflammation in murine models of inflammation.

Here, the authors show that 2’-O-methylated RNA fragments from ribosomal RNA naturally block TLR7 and TLR8, helping to avoid avoid harmful self-RNA detection and autoimmunity.

Activation of the nucleic acid-sensing receptors TLR7 and TLR8 must be tightly regulated, as aberrant activation can result in autoimmune disease. Data now show that endogenous RNA fragments actively impose an allosteric checkpoint on receptor activation.

Biallelic loss-of-function mutations in PLD4, as identified in five patients with SLE, lead to Toll-like receptor-driven hyperactivation of type I interferon, immune cell expansion and autoimmunity.