Evaluation of the hepatic NK cell response during the early phase of Fasciola hepatica infection in rats

Abstract

-The in situ distribution of NK cells in rat liver during the first 28 days of an experimental infection with F. hepatica was investigated. NK cells were distributed homogeneously throughout the hepatic parenchyma in uninfected animals. The total number of hepatic mononuclear cells increased significantly following infection, but the proportion of NK cells did not change. After infection, these cells were found around the portal space, around the centrolobular vein, in the periportal fibrosis and in the band of collagen. However, no NK cells could be detected in or around the granuloma during infection. The frequency of both IL-2-and IFNγ -producing NK cells was higher on day 7 postinfection (pi) but only the percentage of IFNγ + CD161 + subsets remained elevated thereafter, whereas the percentage of both IL-2 + CD161 + and IL-4 + CD161 + subsets returned to the baseline. The number of CD161 + IL10 + cells did not change significantly. These results suggest that NK cells could be another source for the early production of IFNγ but provide no evidence that these cells are involved in early events associated with granuloma formation. Fasciola hepatica / NK cells / cytokine / flow cytometry / immunohistochemistryRésumé -Évaluation de la réponse des cellules NK hépatiques pendant la phase précoce d'infestation par Fasciola hepatica chez le rat. Nous avons suivi la localisation et la distribution hépatique des cellules NK durant les 28 premiers jours d'une fasciolose expérimentale chez le rat. Chez les animaux non infestés, les cellules NK sont distribuées de façon homogène dans tout le foie. Chez les animaux infestés, ces cellules sont localisées préférentiellement au niveau des espaces portes, autour des veines centrolobulaires, dans les bandes de collagène et dans la zone de fibrose péri-portale. En revanche, aucune de ces cellules n'a été détectée ni autour ni au sein du granulome. Le

Immune Suppression in Advanced Chronic Fascioliasis: An Experimental Study in a Rat Model

“…Previous studies of Th cytokines in rats concerned only the early stages of fascioliasis. During the first 2 weeks of infection, F. hepatica induced a transient Th0 cytokine profile, followed by down-regulation of the cellular response and the induction of a Th2 cytokine profile [12,13]. In infected rats, the presence of higher levels of IL-10 and IL-4 at 7 weeks after infection and of IL-10 at 10 weeks after infection was observed, findings that agree with previous observations regarding early infection.…”

“…In the rat, fascioliasis is considered to be an advanced chronic disease from 100 days after infection onward [10,11]. Previous studies performed on T helper cytokines in rats basically concerned the early stages of fascioliasis, suggesting that Fasciola species, similar to other helminth parasites, induce a polarized Th2 response [12][13][14]. However, to our knowledge, no studies have investigated the immune response of Fasciola species in the advanced chronic stage in a rat model.…”

A Secreted Protein from the Human Hookworm Necator americanus Binds Selectively to NK Cells and Induces IFN-γ Production

“…In contrast, several other studies, in which NK cells were depleted by anti-NK1.1 treatment (thus depleting both NK cells and NKT cells), showed no significant impact on host immune responses to Trichuris muris (28) and Schistosoma mansoni (29). Similarly, studies using a rat model of Fasciola hepatica infection concluded that NK cells do not play a significant role in the course of infection (30).…”

Filarial Parasites Induce NK Cell Activation, Type 1 and Type 2 Cytokine Secretion, and Subsequent Apoptotic Cell Death

“…Recently, a secreted protein from the human hookworm Necator americanus was found to bind NK cells directly and induce IFN-␥ production (21). In rodent models of Trichuris muris (22), Schistosoma mansoni (23), and Fasciola hepatica (24), no significant role for NK cells in host immunity has been detected. In a mouse model of Litomosoides sigmodontis infection, NK cells were found to be important in host defense (9), while in a SCID model of B. malayi infection, NK cells were found to be essential for worm development (10).…”