Resumen: Rotaviruses are the leading agents of severe diarrheal disease in infants and young children and complementary strategies to vaccination are needed. Therefore, we evaluated the activity of lactoferrin (LF) from different species against rotavirus in differentiated Caco-2/TC7 cells. The mechanism of rotavirus inhibition and the influence of iron saturation and sialic acid content were also investigated. Furthermore, the effect of bovine LF on Toll-like receptor expression (TLRs) during rotavirus infection was studied. LF presented high inhibitory activity against rotavirus above 8 mg mL−1, the bovine protein being the most potent. The antirotaviral mechanism of LF was mainly related to the virus neutralisation at an early step of infection. Interestingly, a direct relationship between rotavirus neutralisation activity and content of sialic acid in LFs was observed. Finally, the neutralisation of rotavirus by LF leaded to a decreased expression of TLRs in Caco-2/TC7 cells, with a more evident effect on TLR7. Idioma: Inglés DOI: 10.1016/j.idairyj.2023.105818 Año: 2024 Publicado en: INTERNATIONAL DAIRY JOURNAL 149 (2024), 105818 [10 pp.] ISSN: 0958-6946 Financiación: info:eu-repo/grantAgreement/ES/DGA/A20-23R Financiación: info:eu-repo/grantAgreement/EC/H2020/801586/EU/International Doctoral Programme for Talent Attraction to the Campus of International Excellence of the Ebro Valley/IberusTalent Financiación: info:eu-repo/grantAgreement/ES/MINECO/AGL2017-82987-R Tipo y forma: Article (Published version) Área (Departamento): Área Tecnología de Alimentos (Dpto. Produc.Animal Cienc.Ali.)