Host cellular machinery and innate immune pathways

Host cellular machinery and innate immune pathways encompass the collective set of endogenous cellular processes and defense systems that pathogens exploit for replication and that the host utilizes to detect and eliminate threats (Kaufmann et al., 2018, Nature Reviews Drug Discovery). This broad category includes fundamental machinery such as the ribosome for protein translation, intracellular transport networks, and metabolic pathways, as well as the innate immune system's Pattern Recognition Receptors (PRRs) like Toll-like receptors (TLRs) and the cGAS-STING pathway (Janeway & Medzhitov, 2002, Annual Review of Immunology). In therapeutic contexts, these are the focus of host-directed therapies (HDTs), which aim to treat infectious diseases by targeting host factors rather than the pathogen itself, thereby reducing the likelihood of antimicrobial resistance (Zumla et al., 2016, The Lancet Infectious Diseases). For example, JAK inhibitors like baricitinib are used to modulate host inflammatory signaling during severe viral infections, while interferon-based therapies boost innate antiviral states (Richardson et al., 2020, The Lancet). Because these pathways are integral to normal physiological function, pharmacological intervention requires a precise balance to avoid significant toxicity or the disruption of essential cellular homeostasis (Artis & Spits, 2015, Nature).

Other names

Host-directed targetsHost cell factorsInnate immune signaling pathwaysHost-pathogen interfaceHost-directed therapy (HDT) targets

Modulation of host-cell signaling, metabolic, or biosynthetic pathways to inhibit pathogen replication, enhance endogenous defense mechanisms, or normalize the inflammatory response to infection and injury.