Innate immune pattern-recognition receptor (PRR) and downstream signaling pathway (PRR)

Innate immune pattern-recognition receptors (PRRs) are germline-encoded sensors, such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs), that detect pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) (Kawai & Akira, 2010). On monocytes and macrophages, PRR activation triggers the production of pro-inflammatory cytokines and coordinates the transition from innate to adaptive immunity (Janeway & Medzhitov, 2002). Recent studies have demonstrated that PRRs are also expressed on hematopoietic stem cells (HSCs), where they directly sense systemic signals to drive "emergency hematopoiesis" during infection (Chavakis et al., 2019). Chronic or dysregulated PRR signaling in the bone marrow niche is implicated in hematopoietic aging, clonal hematopoiesis, and the development of myeloid malignancies (Jaiswal & Ebert, 2019). Therapeutic strategies include the use of TLR agonists as vaccine adjuvants or cancer immunotherapies to stimulate anti-tumor immunity (Mullard, 2019). Conversely, the development of NLRP3 inflammasome inhibitors and other PRR antagonists aims to treat chronic inflammatory diseases like atherosclerosis and gout. However, targeting these pathways carries significant risks, including systemic inflammation and cytokine release syndrome (Shimabukuro-Vornhagen et al., 2018). Understanding the cell-specific effects of PRR signaling is crucial for developing precision immunotherapies that modulate the innate immune system without causing hematopoietic exhaustion.

Other names

Pattern recognition receptorsInnate immune sensorsPRR signaling pathwaysInnate immune sensing system

Modulation of innate immune sensing through agonism or antagonism of receptors such as TLRs, NLRs, and STING to regulate cytokine production and cellular activation.