Aggregatibacter actinomycetemcomitans , a periodontopathogen, has been associated with several systemic diseases. Herein, we report the protective effect of human lactoferrin (hLF) during A. actinomycetemcomitans bacteremia in lactoferrin knockout (LFKO ^−/− ) mice. The prophylactic, concurrent, and therapeutic intravenous (i.v.) administrations of hLF significantly cleared the bacteria from blood and organs. Nevertheless, all modes of hLF administration significantly decreased the concentrations of serum proinflammatory cytokines, such as interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10, and IL-12p70. Additionally, hLF administration significantly decreased hepatic and splenic proinflammatory cytokine expression levels compared to those in the non-hLF-treated group. Furthermore, administration of hLF decreased the serum C-reactive protein level, inducible nitric oxide synthase (iNOS) and myeloperoxidase (MPO) gene expression levels in liver and spleen. hLF treatment has also resulted in a 6-fold decrease in spleen weight with the migration of typical inflammatory cells in infected mice as a result of decreased inflammatory response. These results reveal that hLF protects against A. actinomycetemcomitans bacteremia, as indicated by rapid bacterial clearance and decreased host proinflammatory mediators.

Aims To 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 Results Antibiotic‐treated immunosuppressed mice were inoculated with C. albicans (or sham infection) by oral swab and evaluated for the severity of infection after 7 days of infection. To determine the protective role of hLF, we added 0·3% 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 = 0·001) 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 = 0·001) 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. Conclusions Human 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 Study Human LF, a multifunctional iron‐binding glycoprotein can be used as a therapeutic active ingredient in oral healthcare products against C. albicans.