AimsTo determine the role of human lactoferrin (hLF) in protecting the oral cavities of mice against Candida albicans infection in lactoferrin knockout (LFKO-/-) mice was compared to wild-type (WT) mice. We also aim to determine the protective role of hLF in LFKO-/- mice. Methods and ResultsAntibiotic-treated immunosuppressed mice were inoculated with C.albicans (or sham infection) by oral swab and evaluated for the severity of infection after 7days of infection. To determine the protective role of hLF, we added 03% solution of hLF to the drinking water given to some of the mice. CFU count, scoring of lesions and microscopic observations were carried out to determine the severity of infection. LFKO-/-I mice showed a 2 log (P=0001) higher CFUs of C.albicans in the oral cavity compared to the WT mice infected with C.albicans (WTI). LFKO-/-I mice given hLF had a 3 log (P=0001) reduction in CFUs in the oral cavity compared to untreated LFKO-/-I mice. The severity of infection, observed by light microscopy, revealed that the tongue of the LFKO-/-I mice showed more white patches compared to WTI and LFKO-/-I+hLF mice. Scanning electron microscopic observations revealed that more filiform papillae were destroyed in LFKO-/-I mice when compared to WTI or LFKO-/-I+hLF mice. ConclusionsHuman LF is important in protecting mice from oral C.albicans infection. Administered hLF may be used to prevent C.albicans infection. Significance and Impact of the StudyHuman LF, a multifunctional iron-binding glycoprotein can be used as a therapeutic active ingredient in oral healthcare products against C.albicans.