Interleukin-12 and protective immunity to schistosomes

Mountford, Adrian P.; Shires, V L; Anderson, Sonia R.

doi:10.1590/s0100-879x1998000100023

Cited by 8 publications

(6 citation statements)

References 21 publications

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“…1998). We speculate that antigenic molecules from lung‐stage parasites have a propensity to stimulate accessory cells to produce IL‐12 and thus favour the polarised development of Th1 cells (Mountford et al . 1997).…”

Section: Introductionmentioning

confidence: 99%

Interleukin‐12 and the host response to parasitic helminths; the paradoxical effect on protective immunity and immunopathology

Mountford

Pearlman

1998

Parasite Immunology

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In general, helminth infections are associated with the development of dominant Th2-mediated immune responses which may be host protective but can also be the cause of immunopathology. Interleukin 12 (IL-12) is known to be a potent inhibitor of Th2 immune responses and as such it might be expected to have an important modulatory role in helminth-induced immune responses. In this review, we discuss the effect of IL-12 on susceptibility to infection, protective immunity and immunopathology, in the context of exposure to a range of helminths including intestinal nematodes, filariae and schistosomes. It is apparent that the effects of IL-12 are complex and can be beneficial as well as detrimental for the host. The precise role of IL-12 depends upon a number of factors including the type of helminth and the specific tissue involved in the inflammatory response.

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Section: Introductionmentioning

confidence: 99%

Interleukin‐12 and the host response to parasitic helminths; the paradoxical effect on protective immunity and immunopathology

Mountford

Pearlman

1998

Parasite Immunology

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“…Unfortunately, the specific type of protective immune response generated by these antigens is frequently discordant between animal and human studies. Th1-type vaccine responses are frequently protective in murine models (33)(34)(35)46), while Th2-type responses are associated with resistance to reinfection in humans (19,32,39). This divergence makes generalizability from animal models of resistance problematic and underscores the importance of well-controlled, immunoepidemiology studies of schistosomiasis in humans.…”

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confidence: 99%

T-Helper-2 Cytokine Responses to Sj97 Predict Resistance to Reinfection withSchistosoma japonicum

Leenstra

Acosta

Wu³

et al. 2006

Infect Immun

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Although schistosomiasis is effectively treated with Praziquantel, rapid reinfection with rebound morbidity precludes effective control based on chemotherapy alone and justifies current efforts to develop vaccines for these parasites. Using a longitudinal treatment-reinfection study design with 616 participants 7 to 30 years of age, we evaluated the relationship between cytokine responses to Schistosoma japonicum soluble adult worm extract (SWAP), Sj97, Sj22.6, and Sj67, measured 4 weeks after treatment with Praziquantel, and resistance to reinfection in a population from Leyte, The Philippines, where S. japonicum is endemic. S. japonicum transmission was high: 54.8% and 91.1% were reinfected within 6 and 18 months, respectively. A Th2 bias in the following cytokine ratios, interleukin-4 (IL-4)/IL-12, IL-5/IL-12, IL-13/IL-12, IL-4/gamma-IFN (IFN-␥), IL-5/ IFN-␥, and IL-13/IFN-␥, in response to SWAP predicted a 1.4-to 2.9-month longer time to reinfection (P < 0.05) and a 27 to 55% lower intensity of reinfection (P < 0.05). Similarly, a Th2 bias in response to Sj97 predicted a 1.6-to 2.2-month longer time to reinfection (P < 0.05) and a 30 to 41% lower intensity of reinfection (P < 0.05). Only a high IL-5/IL-10 ratio in response to Sj22.6 predicted a 3.0-month-longer time to reinfection (P ‫؍‬ 0.03). Cytokine responses to Sj67 were not associated with protection. In a large population-based treatment-reinfection study we found that Th2 responses to SWAP and Sj97 consistently predicted resistance to reinfection. These findings underscore Th2-type immune responses as central in human resistance to S. japonicum and support Sj97 as a leading vaccine candidate for this parasite.

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“…In mansonian schistosomiasis, hepatic fibrosis is initiated by vigorous granulomatous responses to tissueentrapped parasite eggs that is mainly orchestrated by cross-regulatory CD4 + T cell. Although an appropriate 1 response to S. mansoni larvae is associated with high protection levels [17] and 2 response to soluble egg antigens is known to promote excessive fibrotic organ damage [18], there are actually no good or bad T cell responses to Schistosoma larvae or eggs. Earlier studies in experimental schistosomiasis have shown the essential role for CD4 + T cells in granuloma formation and disease [19].…”

Section: Discussionmentioning

confidence: 99%

Preventive CTLA-4-Ig Treatment Reduces Hepatic Egg Load and Hepatic Fibrosis inSchistosoma mansoni-Infected Mice

Sombetzki

Rabes

Bischofsberger

et al. 2019

BioMed Research International

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Background. Hepatic fibrosis and granuloma formation as a consequence of tissue entrapped eggs produced by female schistosomes characterize the pathology of Schistosoma mansoni infection. We have previously shown that single-sex infection with female schistosomes mitigates hepatic fibrosis after secondary infection. This was associated with an increased expression of cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), known as a negative regulator of T cell activation. Based on these findings, we hypothesized that administration of agonistic CTLA-4-Ig (Belatacept) is capable to prevent and/or treat hepatic fibrosis during schistosomiasis. Methods. Mice were infected with 50 S. mansoni cercariae and CTLA-4-Ig, or appropriated control-Ig was administered for 4 weeks. Preventive treatment started 4 weeks after infection, before onset of egg production, and therapeutic treatment started 8 weeks after infection when hepatic fibrosis was already established. Results. When given early after infection, livers of CTLA-4-Ig-treated mice showed significantly reduced collagen deposition and decreased expression of profibrotic genes in comparison to controls. In addition, administration of CTLA-4-Ig suppressed the inflammatory T cell response in infected mice. If therapy was started at a later time point when fibrogenesis was initiated, CTLA-4-Ig had no impact on hepatic fibrosis. Conclusion. We could demonstrate that an early preventive administration of CTLA-4-Ig suppresses effector T cell function and therefore ameliorates liver fibrosis. CTLA-4-Ig administration after onset of egg production fails to treat hepatic fibrosis.

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Interleukin-12 and protective immunity to schistosomes

Cited by 8 publications

References 21 publications

Interleukin‐12 and the host response to parasitic helminths; the paradoxical effect on protective immunity and immunopathology

Interleukin‐12 and the host response to parasitic helminths; the paradoxical effect on protective immunity and immunopathology

T-Helper-2 Cytokine Responses to Sj97 Predict Resistance to Reinfection withSchistosoma japonicum

Preventive CTLA-4-Ig Treatment Reduces Hepatic Egg Load and Hepatic Fibrosis inSchistosoma mansoni-Infected Mice

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