Role of Toll-like Receptor-9 in Lung Injury

Toll-like receptors (TLRs) are pathogen associated molecular pattern (PAMP) receptors that are expressed by several cells of the innate and adaptive immune systems. TLR-9, also referred to as CD289, is localized in the endosomal compartment and recognizes specific unmethylated CpG motifs prevalent in microbial but not vertebrate genomic DNA. Activation of TLR-9 results in an inflammatory response, ultimately via a Th1-based pathway. TLR-9 is known to play a critical role in mediating the inflammatory response to lung injury. Due to its significant circulating blood volume and continuous exposure to the external environment, the lung is constantly exposed to potentially injurious agents that may trigger a common final pathway causing acute lung injury (ALI) or its more severe form, acute respiratory distress syndrome (ARDS). Both conditions result in a marked increase in inflammatory cytokines, such as TNFα, IL-1β and IL-6, and can result in significant morbidity and mortality. Prior studies have demonstrated the role of TLR-9 in sepsis and lung injury, focusing on its interactions with artificial CpG DNA and the potential positive immunomodulatory benefits from inhibition. In this review, we discuss the role of TLR-9 in the pathogenesis and treatment of lung injury. J Nat Sci, 5(2):e551, 2019