{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T21:02:24Z","timestamp":1793826144918,"version":"4.6.1"},"reference-count":207,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Alphavirus chikungunya (CHIKV) is an arthritogenic virus whose innate recognition is primarily driven by pathogen associated molecular patterns (PAMPs) or damage associated molecular patterns (DAMPs), sensed by a variety of pattern recognition receptors (PRRs) such as Toll-like receptors (TLR), and cytosolic RIG-like receptors. CHIKV infection elicits a multifaceted interplay between viral replication strategies and host innate immune recognition. Among these pathways, TLR-mediated sensing emerges as a central axis of antiviral defense, orchestrating type I interferon responses and inflammatory cascades that determine the balance between viral clearance and immunopathology. In parallel, inflammasomes such as NLRP3 amplify the IL-1\u03b2\/IL-18 axis, being a major contributing factor for the establishment of chronic joint inflammation. The transition from self-limited rapid resolving infection to chronic disease is largely determined by the cytokine and chemokine milieu. It is known that acute infection is characterized by high levels of IL-6, TNF-\u03b1, and IL-1\u03b2, which drive fever, myalgia, and joint inflammation; and chemokines such as CCL2 (MCP-1) were shown to recruit monocytes and macrophages to inflamed joints, whereas CXCL9\/10 (MIG\/IP-10) enhance T-cell trafficking, contributing to viral clearance but also sustaining tissue inflammation. In this review, we aim to consolidate the current knowledge on the molecular pathways that sense CHIKV infection and trigger the antiviral innate response that can act as both protective and pathogenic. By integrating viral evasion strategies and host factors, we provide a comprehensive framework for understanding innate immunity in CHIKV infection, its implications for therapeutic design, and important gaps that can guide future studies.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1810208","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T06:02:51Z","timestamp":1777442571000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Innate immune sensing of alphavirus chikungunya: balancing antiviral defense and pathogenesis"],"prefix":"10.3389","volume":"17","author":[{"given":"Juliane Santos de Fran\u00e7a","family":"da Silva","sequence":"first","affiliation":[{"name":"Department of Microbiology and Parasitology, Biosciences Center, Federal University of Rio Grande do Norte, Natal","place":["Rio Grande Do Norte, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9lio Valdevino","family":"Ferreira Junior","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, Biosciences Center, Federal University of Rio Grande do Norte, Natal","place":["Rio Grande Do Norte, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livian Maria Silva","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, Biosciences Center, Federal University of Rio Grande do Norte, Natal","place":["Rio Grande Do Norte, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valter Feirreira de","family":"Andrade-Neto","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, Biosciences Center, Federal University of Rio Grande do Norte, Natal","place":["Rio Grande Do Norte, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Marcos da Matta","family":"Guedes","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, Biosciences Center, Federal University of Rio Grande do Norte, Natal","place":["Rio Grande Do Norte, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana Navarro Ueda","family":"Yaochite","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Dentistry & Nursing, Federal University of Cear\u00e1","place":["Fortaleza, Cear\u00e1, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Freitas De Oliveira","family":"Fran\u00e7a","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Medicine. 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