The killer effect of lactoferrin in Giardia lamblia involves critical morphological defects

FRONTERA L; LANFREDI-RANGEL; TOUZ MC

Congreso; LI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular. SAIB.; 2016

Lactoferrin (LF) is an 80 KDa iron-binding glycoprotein that plays a significant role in the innate immune system and is considered to be an important microbicide molecule. LF is effective in the treatment of giardiasis, an intestinal infection caused by the protozoan parasiteG. lamblia. However, the molecular mechanisms by which LF exerts its effect on this parasite are not known. Most of the microbicidal activity of human or bovine LF (hLF or bLF) has been localized at the N-terminal region of the mature LF (lactoferricin: LFcin). LFcin is produced by pepsin cleavage of the native proteinin vitroand likelyin vivo. In this work, we analyze the participation of the endocytic machinery ofG. lambliain the internalization of LF and LFcin and their effects in cell homeostasis. To this end, we have developed several tools including the stable expression of dominant negative mutants, knock-down strains, specific antibodies, and the use of confocal and electron microscopy. Our results showed that LF and LFcin are internalized by receptor-mediated endocytosis and produces morphological changes in the lysosomal-peripheral vacuoles, altering their content and acidifying the cytoplasm of the cell. Our findings will contribute to disclose the fine mechanism in which LF and LFcin might function as an antigiardial molecule.