Entamoeba histolytica is an invasive enteric protozoan, whose
infections are associated to high morbidity and mortality rates. However, only less than 10% of infected patients develop invasive
amebiasis. The ability of E. histolytica to adapt to the intestinal microenvironment could be determinant in triggering pathogenic behavior. Indeed, during chronic
inflammation, the vagus nerve limits the immune response through the anti-inflammatory reflex, which includes
acetylcholine (ACh) as one of the predominant
neurotransmitters at the
infection site. Consequently, the response of E. histolytica trophozoites to ACh could be implicated in the establishment of invasive disease. The aim of this study was to evaluate the effect of ACh on E. histolytica virulence. Methods include binding detection of ACh to plasma membrane, quantification of the relative expression of
virulence factors by RT-PCR and western blot, evaluation of the effect of ACh in different cellular processes related to E. histolytica pathogenesis, and assessment of the capability of E. histolytica to migrate and form
hepatic abscesses in hamsters. Results demonstrated that E. histolytica trophozoites bind ACh on their membrane and show a clear increase of the expression of
virulence factors, that were upregulated upon stimulation with the
neurotransmitter. ACh treatment increased the expression of L220,
Gal/GalNAc lectin heavy subunit (170 kDa),
amebapore C,
cysteine proteinase 2 (ehcp-a2), and
cysteine proteinase 5 (ehcp-a5). Moreover, erythrophagocytosis, cytotoxicity, and actin cytoskeleton remodeling were augmented after ACh treatment. Likewise, by assessing the formation of
amebic liver abscess, we found that stimulated trophozoites to develop greater hamster hepatic lesions with multiple
granulomas. In conclusion, ACh enhanced parasite pathogenicity by upregulating diverse
virulence factors, thereby contributing to disease severity, and could be linked to the establishment of invasive
amebiasis.