Lactoferrin modulation of antigen-presenting-cell response to BCG infection

Lactoferrin, an 80-kDa basic N-glycoprotein, has been identified as a potent immune modulator. When used experimentally as an adjuvant in mice, lactoferrin can boost the efficacy of the BCG vaccine to increase delayed type hypersensitive responses and to limit subsequent pathology upon infection with virulent mycobacterium. These studies outline preliminary findings to examine the multiple mechanisms of action of lactoferrin on antigen-presenting cells which would enhance vaccination and bridge the innate and adaptive responses.

Bone marrow-derived macrophages (BMMs) and human and murine cells lines were infected with BCG in the presence or absence of bovine lactoferrin. The cells were examined for changes in uptake of BCG post infection and increases in the surface expressions of Class I or Class II molecules by flow cytometric analysis. Infected cultures were collected to examine cytokine production by ELISA.

Lactoferrin was found to significantly increase the uptake of BCG organisms during infection of BMMs and human monocyte cell lines. Lactoferrin added to BCG-infected BMMs demonstrated significantly increased surface expression of Class II (I-Ab), but no change in Class I (H-2kb) molecules. In addition, BCG-infected cells incubated in the presence of lactoferrin demonstrated a significant increase in relative IL-12 to IL-10 ratios in a dose-dependent manner.

Overall, lactoferrin was able to alter BCG-infected antigen-presenting cells (APCs) in vitroin a manner consistent with the induction of responses required for successful presentation of antigen to the adaptive arm of the immune response, which would lead to the generation of strong T-helper 1 type immunity.