Lymphocyte and cytokine responses of young cattle during primary infection with Fasciola hepatica

Clery, Daniel; Mulcahy, Grace

doi:10.1016/s0034-5288(98)90171-0

Cited by 37 publications

(28 citation statements)

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“…We have previously detected IL-12 mRNA on day 7 pi [27], which may account for the production of both Th1 and Th2 cytokines by HMNC. This is consistent with other studies on the peripheral response of mammals infected with F. hepatica, which was found to involve an early Th1/Th0 cytokine profile [5,6,18,21,22]. However, our results concerning IFN-γ levels are of particular interest.…”

Section: Discussionsupporting

confidence: 93%

Early hepatic immune response in rats infected with Fasciola hepatica

et al. 2002

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-We investigated the phenotype of the T cells (CD4 + and CD8 + ) that produced Th1 (IFN-γ ) and Th2 cytokines (IL-4 and IL-10) during the first two weeks of experimental fasciolosis in rats. We also followed the kinetics of the cytokine and proliferative responses of hepatic mononuclear cells (HMNC) over the same period. We found that HMNC were more numerous in the infected animals than in the controls. The percentage of CD4 + cells increased significantly after infection, whereas the percentage of CD8 + cells did not change. Moreover, the frequency of the cells producing (CP) cytokine changed after infection. The frequency of CP IFN-γ on 7 days postinfection (pi) was similar to that in control animals. However, the frequency of CP IFN-γ was clearly lower on day 14 pi, whereas the frequency of CP IL-4 and CP IL-10 had increased. The CP IL-10-were mostly CD4 + . Mitogenic stimulation (phorbol myristate acetate/ionomycin) of HMNC led to an increase in the amounts of the Th2 cytokines in the supernatant on days 7 and 14 pi, with the increase more pronounced on day 14. In contrast, IFN-γ levels also increased by day 7 pi but then decreased to below control levels by day 14. In addition, HMNC proliferation in response to mitogen followed a similar pattern to IFN-γ production. These findings suggested that, during the first 2 weeks of infection, F. hepatica induced a transient Th0 cytokine profile followed by downregulation of the cellular response and the induction of a Th2 cytokine profile.Fasciola hepatica / rat / cytokine / liver / lymphocytes Résumé -Réponse immunitaire hépatique précoce chez le rat infesté par Fasciola hepatica. Nous avons caractérisé le phénotype des sous-populations lymphocytaires T (CD4 + , CD8 + ) qui produisent des cytokines de type Th1 (IFN-γ ) et Th2 (IL-4, IL-10) au cours de l'infestation expérimen-tale par F. hepatica chez le rat (phase précoce). Nous avons aussi suivi la production des cytokines et (33) 2 47 42 77 74; e-mail: sibille@tours.inra.fr la réponse proliférative des cellules mononucléaires hépatiques (CMNH) après une stimulation in vitro par des mitogènes (phorbol myristate acetate) et par des antigènes spécifiques (les produits d'excrétion-sécrétion de F. hepatica). Le pourcentage des cellules CD4 + augmente après infestation tandis que celui des cellules CD8 + demeure inchangé. Après infestation, la fréquence des cellules productrices (CP) de cytokine change. Tandis qu'au 7 e jour après infestation (JAI) la fréquence des CP d'IFN-γ reste identique à celles des animaux témoins, elle est nettement plus basse au 14 e JAI ; la fréquence des CP d'IL-4 et des CP d'IL-10 augmente (surtout les CD4 + IL-10 + , notamment au 14 e JAI). En outre, dans les surnageants de culture des CMNH, la production de cytokines de type Th2 est accrue au 7 e JAI et plus importante encore au 14 e JAI. Le niveau de production d'IFN-γ augmente au 7 e JAI mais décroît jusqu'à devenir inférieure à celle du témoin au 14 e JAI. De plus, la ré-ponse proliférative est plus importante au 7 e JAI mais...

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Section: Discussionsupporting

confidence: 93%

Early hepatic immune response in rats infected with Fasciola hepatica

et al. 2002

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“…Although the variation between individual animals was observed. Other results shows that IFN-γ secretion by whole blood cultures from trickle infected calves, stimulated with adult and immature F. hepatica antigens, reaches a maximum 2 to 5 weeks post infection (Clery and Mulcahy 1998). Those results, supported by ours (BOMAC cells secreted neither IL-4, nor IFN-γ upon stimulation with Fh-ES), would suggest that host immune cells need to be previously stimulated by other parasite antigens during course of infection.…”

Section: Discussionsupporting

confidence: 68%

Fasciola hepatica — the pilot study of in vitro assessing immune response against native and recombinant antigens of the fluke

Bąska

Zawistowska-Deniziak

Zdziarska

et al. 2013

Acta Parasitologica

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Fasciola hepatica is a liver fluke that infects 2.4 million of people and causes great economical loss in animal production. To date a 100% effective vaccine has not been developed and the disease is controlled by drug therapy. Great efforts are put into development of effective vaccine against parasite what is difficult since Fasciola spp. (like other helmints) during evolutionary process has developed sophisticated and efficient methods to evade immune response. During preliminary experiments it is convenient to use cell lines which are relatively cheap and allow for reproducible comparison of results between laboratories. We stimulated BOMA (bovine monocyte/macrophage cell line) and BOMAC (bovine macrophage cell line) with native or recombinant antigens of Fasciola hepatica and assessed IFN-γ, IL-4 and TNF-α level upon stimulation. We observed diminished secretion of proinflammatory TNF-α in LPS activated BOMA cells stimulated with Excretory/Secretory products of adult fluke (Fh-ES). We also observed greater changes in gene expression in LPS activated BOMA cells than in non activated BOMA cells upon stimulation using Fh-ES. The results show possibility of using cell lines for in vitro research of bovine immune response against liver fluke, although this model still requires validation and further characterization.

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“…This is similar to other helminth infections where chronic infections occur. Previous work detailing the immune response of F. hepatica-infected animals demonstrated a strong Th2 bias, characterized by high immunoglobulin G1 production coupled with poor IFN-␥ release and cellular proliferation by 4 weeks postinfection (5,6). The results presented here, describing the kinetics of IL-4 and IL-10 production from animals infected with F. hepatica, add to the knowledge of immune responses to F. hepatica.…”

Section: Discussionmentioning

confidence: 52%

“…In experimentally infected cattle, gamma interferon (IFN-␥) production and cellular proliferation are detected soon after infection in response to both F. hepatica antigen and the mitogen concanavalin A. However, in response to both these stimuli, cellular proliferation and IFN-␥ production decrease as infection progresses, and when an animal enters the chronic stage of infection, these responses are no longer detectable (6). These highly polarized immune responses may be associated with increased host susceptibility to other pathogens.…”

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confidence: 99%

Possible Role for Toll-Like Receptors in Interaction ofFasciola hepaticaExcretory/Secretory Products with Bovine Macrophages

Flynn¹,

Mulcahy²

2008

Infect Immun

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Alternative activation of macrophages (M) during helminth infection is a characteristic feature of the host immune response. Alternatively activated macrophages (AAM) are distinguished from others by high arginase 1 (Arg-1) activity, low nitric oxide (NO), and high interleukin 10 (IL-10) production. In murine models, these cells have been shown to possess anti-inflammatory properties. They have also been implicated in exacerbating a subsequent infection with a secondary pathogen. In this study we used cattle experimentally infected with Fasciola hepatica to monitor the kinetics of IL-4 and IL-10 over the course of infection. Using naïve M in vitro, we examined the effects of exposure to F. hepatica excretory/secretory products (FhepES) alone or in combination with IL-4. Our results suggest that FhepES may work in combination with IL-4 to produce AAM. The effects of FhepES on the subsequent responses to lipopolysaccharide (LPS) and purified protein derivative from Mycobacterium bovis (PPD-B), which are bovine Toll-like receptor 4 (TLR4) and TLR2 antagonists, respectively, were also examined. We found that M stimulated with FhepES together with LPS or PPD-B have reduced NO or gamma interferon production, respectively. The ability of FhepES to produce AAM was found to be heat labile and partially dependent on glycan residues. A possible role for TLR recognition is discussed.Alternative activation of macrophages (M) is a common feature of the immune response to helminth parasites, and their presence has been shown in a number of model infections, including those caused by Schistosoma mansoni (14), Taenia crassiceps (25), Brugia malayi (21), and Fasciola hepatica (9, 11). These alternatively activated macrophages (AAM) are distinguished from classically activated macrophages by preferential use of arginase 1 (Arg-1), instead of inducible nitric oxide (13), to metabolize L-arginine. A number of other markers of AAM have also been identified; these include increased expression of interleukin 10 (IL-10) and the mannose receptor (13), as well as production of intelectin, chitinases, and chitinase-like proteins (22).Immune responses to helminth infections are often polarized toward the Th2 end of the immune spectrum. These polarized responses may be associated with the development of chronic infections while avoiding parasite clearance by the host (20). Th2-dominated responses have been observed in F. hepatica infection in both mice and the natural ruminant hosts. Antibody production is dominated by the immunoglobulin G1 isotype (5, 23). In experimentally infected cattle, gamma interferon (IFN-␥) production and cellular proliferation are detected soon after infection in response to both F. hepatica antigen and the mitogen concanavalin A. However, in response to both these stimuli, cellular proliferation and IFN-␥ production decrease as infection progresses, and when an animal enters the chronic stage of infection, these responses are no longer detectable (6). These highly polarized immune responses may be associated with ...

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Lymphocyte and cytokine responses of young cattle during primary infection with Fasciola hepatica

Cited by 37 publications

References 12 publications

Early hepatic immune response in rats infected with Fasciola hepatica

Early hepatic immune response in rats infected with Fasciola hepatica

Fasciola hepatica — the pilot study of in vitro assessing immune response against native and recombinant antigens of the fluke

Possible Role for Toll-Like Receptors in Interaction ofFasciola hepaticaExcretory/Secretory Products with Bovine Macrophages

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