Holding the Inflammatory System in Check: TLRs and NLRs

Aberrant inflammation has been linked to the development of a diverse spectrum of human diseases. We now appreciate that Toll-like receptor (TLR) and Nod-like receptor (NLR) signaling pathways play an important role in the onset and/or severity of these pathologies, and targeting of these receptors has shown promise in preclinical studies of infectious diseases, autoimmune disorders, tissue injury, and cancer. Recently, clinical trials have been initiated to establish the efficacy of compounds targeting TLR and NLR pathways to improve disease outcomes. Despite advancements in the field, major challenges remain in potential ways to target these receptors at various stages of disease pathogenesis and develop effective therapeutics. The articles contained in this special issue include reviews, translational studies, and basic science findings that are focused on characterizing the contribution and molecular mechanisms associated with TLR and NLR signaling in diverse disease processes. Together, these studies serve to illustrate the essential role that these pattern recognition receptors play in maintaining immune system homeostasis in both human disease pathobiology and preclinical animal models. In particular, this special issue emphasizes the role of TLRs and NLRs in modulating signaling pathways associated with inflammatory disease processes and cytokine production. For example, in the article entitled " Effect of Toll-Like Receptor 4 on Synovial Injury of Temporomandibular Joint in Rats Caused by Occlusal Interference " by J. Kong et al., the authors show that activation of TLR4 participates in the initiation and development of synovial membrane inflammation by regulating the expression of inflammatory mediators like IL-1í µí»½. This inflammation reaction and increased IL-1í µí»½ could be restrained by treatment with a TLR4 signaling inhibitor. In addition to TLR signaling and synovial injury, the importance of NLR family members is also explored in a series of articles evaluating their contribution either following traumatic brain injury (TBI) or in the context of parasite infection. There are currently several therapeutics targeting NLR family members under development to treat or attenuate brain injury following trauma. In this special issue, T. Brickler and colleagues examine the role of the NLRP1 inflammasome in TBI. In their article entitled " Nonessential Role for the NLRP1 Inflammasome Complex in a Murine Model of Traumatic Brain Injury " the authors conclude that the NLRP1 inflammasome has only a minor role in TBI using a moderate controlled cortical impact injury model. While some cytokine expression differences were observed in Nlrp1 −/− mice, these animals showed no …