Modulation of intestinal innate immune response by Giardia intestinalis

HUMEN, M; MORENO, G; GONZALEZ MACIEL, D; PÉREZ, P; RUMBO, M

Ciudad autónoma de Buenos Aires

Congreso; First French-Argentine Immunology Congress - LVIII Reunión Anual de la Sociedad Argentina de Inmunología; 2010

Giardia intestinalis is the etiological agent of giardiasis, one of the most frequent intestinal diseases worldwide that may present from mild symptoms to severe and protracted diarrhea. The specific mechanisms of pathogenicity and the major host defenses against Giardia infection still remain unclear. In the present work, we sought to gain insight in the activation and modulation of chemokine production by intestinal mucosa upon Giardia infection, using in vitro and in vivo models. In order to evaluate the expression of chemokines (CCL20, CXCL10 and CXCL2), cultured enterocyte-like Caco-2 cells were infected with Giardia trophozoites and 4 h later RNA levels were measured by QPCR and normalized to actin. There was a nearly 9-fold (9,18 ± 3,58) increase in CCL20 expression in infected cells.  In addition, we assessed the expression in vivo of CCL20 using C57BL/6 infected mice. Giardia trophozoites (strain GS/H7) were administrated, and 2 h or 7 days post-infection duodenum samples were analyzed by QPCR. There was an 11-fold (10,98 ± 3,07) increase in CCL20 expression 2 h post-infection in infected animals compared with uninfected controls. No induction was detected at 7 days post-infection, coincident with no inflammatory alterations in the mucosa. We used a reporter Caco-2 cell line harboring the luciferase gene under the control of the CCL20 promoter to evaluate the modulation of innate response by Giardia infection when co-administered with flagellin, a TLR5 ligand that is an inflammatory stimuli to intestinal epithelial cell. In this format, dose- and strain-dependent inhibition of luciferase production was evidenced. Infection of Giardia 1h previous to flagellin administration showed an even more pronounced inhibition in the reporter activity. In view of these results Giardia intestinalis triggers a transient activation of mucosal innate response but can also modulate the production of proinflammatory chemokines triggered by the activation of innate receptors.