Increased Interleukin-4 and Interleukin-5 Production in Response to Schistosoma haematobium Adult Worm Antigens Correlates with Lack of Reinfection after Treatment

Medhat, Ahmed; Shehata, Mohammed; Bucci, Kim; Mohamed, Shoari; Dief, Ahmed Diab Enas; Badary, Saad; Galal, Hesham; Nafeh, Mohamed; King, Christopher L.

doi:10.1086/515630

Cited by 70 publications

(70 citation statements)

References 44 publications

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“…However, in the murine host, multiple vaccinations fail to boost cell-mediated immunity but progressively enhance the humoral arm of the protective response (13,31). Further evidence for the importance of type 2-mediated effector mechanisms comes from human patients, where a correlation exists between IL-4 and IL-5 production by PBMC and resistance to reinfection after drug treatment (40,53). It has to be noted that in humans, IgE and IgA antibodies have been postulated to participate in protective immunity (20,26,27).…”

Section: Discussionmentioning

confidence: 99%

Cellular and Humoral Immune Responses and Protection against Schistosomes Induced by a Radiation-Attenuated Vaccine in Chimpanzees

et al. 2001

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The radiation-attenuated Schistosoma mansoni vaccine is highly effective in rodents and primates but has never been tested in humans, primarily for safety reasons. To strengthen its status as a paradigm for a human recombinant antigen vaccine, we have undertaken a small-scale vaccination and challenge experiment in chimpanzees (Pan troglodytes). Immunological, clinical, and parasitological parameters were measured in three animals after multiple vaccinations, together with three controls, during the acute and chronic stages of challenge infection up to chemotherapeutic cure. Vaccination induced a strong in vitro proliferative response and early gamma interferon production, but type 2 cytokines were dominant by the time of challenge. The controls showed little response to challenge infection before the acute stage of the disease, initiated by egg deposition. In contrast, the responses of vaccinated animals were muted throughout the challenge period. Vaccination also induced parasite-specific immunoglobulin M (IgM) and IgG, which reached high levels at the time of challenge, while in control animals levels did not rise markedly before egg deposition. The protective effects of vaccination were manifested as an amelioration of acute disease and overall morbidity, revealed by differences in gamma-glutamyl transferase level, leukocytosis, eosinophilia, and hematocrit. Moreover, vaccinated chimpanzees had a 46% lower level of circulating cathodic antigen and a 38% reduction in fecal egg output, compared to controls, during the chronic phase of infection.

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Section: Discussionmentioning

confidence: 99%

Cellular and Humoral Immune Responses and Protection against Schistosomes Induced by a Radiation-Attenuated Vaccine in Chimpanzees

et al. 2001

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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%

“…The association of Th2 responses and resistance to schistosome infection in humans has been observed for eosinophilia (24), anti-parasite IgE (17,19,38), and peripheral blood mononuclear cell (PBMC) production of interleukin-4 (IL-4) and IL-5 in response to crude parasite extracts (32,39). Despite broad acceptance of the paradigm, Th2 cytokine responses to specific parasite antigens have been prospectively associated with resistance to reinfection after PZQ treatment in only a single study in S. mansoni (3).…”

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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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“…However, more recent studies suggest that the situation is more complicated, showing that schistosome infections in mice with reduced type 2 responsiveness lead to a more severe pathological outcome than in mice capable of mounting type 2 responses [14]. In agreement with the more recent studies, immuno-epidemiological studies of human populations in endemic areas have revealed a positive correlation between high, specific immunoglobulin (Ig) E levels, eosinophilia, interleukin (IL)-5 levels and resistance to reinfection after treatment [30,48]. However, high levels of gamma interferon (IFN-γ) and tumor necrosis factor (TNF) together with lower levels of IL-5 seem to be associated with hepatosplenic disease [33].…”

Section: Introductionmentioning

confidence: 52%

“…Th2 responses, although related to hepatic fibrosis, seem to be associated with reduced susceptibility and host protection against overt human hepatosplenic disease due to inflammatory responses [25,30,33]. Indeed, also porcine IL-4 has been shown to play an important role in the regulation of macrophage mediated inflammatory responses [49].…”

Section: Discussionmentioning

confidence: 99%

Cytokine mRNA profiles in pigs exposed prenatally and postnatally toSchistosoma japonicum

Techau¹,

Johansen²,

Aasted

et al. 2007

Vet. Res.

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-The pig is a natural host for Schistosoma japonicum and a useful animal model of human infection. The aim of the present study was to assess the differences between the cytokine profiles in prenatally or postnatally S. japonicum exposed pigs. Seven prenatally exposed pigs, 7 postnatally exposed pigs and 4 uninfected control pigs were compared 27 weeks post exposure. Variables included worm burdens, tissue egg counts, liver pathology and mRNA levels of IL-2, IL-4, IL-10, IL-12, TNF-α, TGF-β1 and IFN-γ in the liver and the caecum, assessed by RT-PCR. Infection intensity and level of septal fibrosis were significantly higher in the postnatal group compared to the prenatal group (P < 0.05). A significant increase of IL-4 (P < 0.01), IL-10 (P < 0.01), IL-12 (P < 0.01) and TNF-α (P < 0.05) mRNA level was also observed in the caecum of prenatally infected animals compared to the control group (P < 0.01). The prenatal group showed higher levels of TGF-β1 in the liver compared with the postnatally infected group (P < 0.05) and the control group (P < 0.01). This suppressive immune response correlated with previously reported low hepatic pathogenesis in prenatally exposed pigs.swine / Schistosoma japonicum / cytokine / prenatal infection / postnatal infection

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Increased Interleukin-4 and Interleukin-5 Production in Response to Schistosoma haematobium Adult Worm Antigens Correlates with Lack of Reinfection after Treatment

Cited by 70 publications

References 44 publications

Cellular and Humoral Immune Responses and Protection against Schistosomes Induced by a Radiation-Attenuated Vaccine in Chimpanzees

Cellular and Humoral Immune Responses and Protection against Schistosomes Induced by a Radiation-Attenuated Vaccine in Chimpanzees

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

Cytokine mRNA profiles in pigs exposed prenatally and postnatally toSchistosoma japonicum

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