The emerging role of TLR7-mediated signaling in respiratory viral infections and autoimmune diseases.

Toll-like receptor 7 (TLR7) is a key endosomal sensor that detects single-stranded RNA, linking innate and adaptive immunity through the induction of type I interferons and proinflammatory cytokines. Recent studies have underscored the pivotal role of TLR7 in shaping immune responses to respiratory viral infections, including SARS-CoV-2, influenza A virus, and respiratory syncytial virus (RSV), as well as in the pathogenesis of systemic autoimmune diseases such as systemic lupus erythematosus (SLE), which can be triggered by the respiratory viral infections. In COVID-19, TLR7 deficiency is associated with severe disease, particularly in males, due to impaired interferon responses and antibody production. In influenza, TLR7 enhances humoral and cytotoxic responses, though its overactivation may contribute to immunopathology. The role of TLR7 in RSV remains controversial, with both protective and detrimental effects reported depending on host and experimental context. In contrast, TLR7 plays a pathogenic role in SLE by amplifying type I interferon signaling and promoting autoreactive B cell activation. This review synthesizes current knowledge on TLR7-mediated signaling across these diseases, highlighting its context-dependent functions and dualistic nature in immunity and disease. We will discuss mechanistic insights, clinical relevance, and emerging therapeutic strategies targeting TLR7, emphasizing the need for precision modulation of this pathway in the treatment of viral infections and autoimmune disorders.