Mechanisms of resistance to S. mansoni infection: the rat model

Khalife, Jamal; Cêtre, Catherine; Pierrot, Christine; Capron, Moníque

doi:10.1016/s1383-5769(00)00059-3

Cited by 40 publications

(49 citation statements)

References 36 publications

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“…These findings oppose the dogma that eosinophils are the key cells that play a critical role eliminating helminths (7,20,21,29). In contrast, our data favor a possible active participation of macrophages in eliminating T. crassiceps, perhaps by producing NO.…”

Section: T Crassiceps-infected Stat6contrasting

confidence: 95%

“…Similar differences were observed in the levels of total IgG1 and IgG2a (data not shown). Although Th2-associated IgE has been shown to play a role in mediating immunity against helminths (20,21), we found that T. crassiceps-infected STAT6 Ϫ/Ϫ mice efficiently controlled parasite burdens despite producing significantly lower levels of IgE as compared with similarly infected STAT6 ϩ/ϩ mice, suggesting that IgE may have a limited role in mediating protective immunity against T. crassiceps (Fig. 2c).…”

Section: T Crassiceps-infected Stat6mentioning

confidence: 77%

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Cutting Edge: Susceptibility to the Larval Stage of the Helminth ParasiteTaenia crassicepsIs Mediated by Th2 Response Induced Via STAT6 Signaling

Rodrı́guez-Sosa

David

Bojalil

et al. 2002

The Journal of Immunology

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Using STAT6−/− BALB/c mice, we analyzed the role of STAT6-induced Th2 response in determining the outcome of murine cysticercosis caused by the helminth parasite Taenia crassiceps. After T. crassiceps infection, wild-type BALB/c mice developed a strong Th2-like response; produced high levels of IgG1, IgE, IL-4, as well as IL-13; and remained susceptible to T. crassiceps. In contrast, similarly infected STAT6−/− mice mounted a strong Th1-like response; produced high levels of IgG2a, IL-12, IFN-γ, as well as nitric oxide; and efficiently controlled T. crassiceps infection. These findings demonstrate that Th2-like response induced via STAT6-mediated signaling pathway mediates susceptibility to T. crassiceps and, furthermore, that unlike the case in most helminths, immunity against T. crassiceps is mediated by a Th1-like rather than Th2-like response.

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Section: T Crassiceps-infected Stat6contrasting

confidence: 95%

Section: T Crassiceps-infected Stat6mentioning

confidence: 77%

Cutting Edge: Susceptibility to the Larval Stage of the Helminth ParasiteTaenia crassicepsIs Mediated by Th2 Response Induced Via STAT6 Signaling

Rodrı́guez-Sosa

David

Bojalil

et al. 2002

The Journal of Immunology

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“…Typically SEA-specific immune responses in experimentally infected mice coincide with the onset of egg laying, when infected animals are exposed to egg-derived antigens (14). This contrasts sharply with what is seen during experimental infections of rats, during which worms die within 4 weeks of infection before egg laying takes place, but specific Th2 responses still predominate (20). During chronic human infections, immune responses to SEA and SWA may interact and influence each other.…”

Section: Discussionmentioning

confidence: 58%

Cytokine Production in Whole Blood Cultures from a Fishing Community in an Area of High Endemicity forSchistosoma mansoniin Uganda: the Differential Effect of Parasite Worm and Egg Antigens

et al. 2004

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The human host is continuously exposed to the egg and the adult worm developmental stages of Schistosoma mansoni during chronic infections with the parasite. To assess the cytokine responses induced by these different costimulating stages and how they are influenced by host age and infection intensity, whole blood samples from a cross-sectional cohort of 226 members of a Ugandan fishing community who had been resident in an area with high transmission of S. mansoni for the previous 10 years or from birth were stimulated with S. mansoni egg antigen (SEA) or worm antigen (SWA). SWA-specific gamma interferon (IFN-␥) production increased with age, and the levels of SWA-and SEA-specific interleukin 3 (IL-3) were weakly correlated with schistosome infection intensity. The production of most cytokines was little affected by age or infection intensity but was either SEA or SWA specific. One hundred thirty-two members of the cohort coproduced IL-5 and IL-13 specifically in response to SWA, whereas only 15 produced these cytokines, and at much lower levels, in response to SEA. IL-10, IL-4, and IFN-␥ were also produced in response to SWA, whereas the response to SEA consisted almost exclusively of IL-10. Our results suggest that, in contrast to what has been described for the murine model of S. mansoni and during acute human infections, chronic intense exposure to and infection with S. mansoni in this cohort resulted in very low levels of response to SEA in vitro in the presence of a vigorous and mixed Th1-Th2 response to SWA.

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“…Although the exact role of the IgE responses remains to be elucidated, there is always the possibility that the presence of high levels of IgE might be associated with high risk of anaphylaxis, particularly in individuals with atopic predisposition (33). On the other hand, antigenspecific IgE appears to correlate with protection in diseases such as schistosomiasis (17). Since mutants LTR72 and LTK63 were found to be highly immunogenic, the LT challenge mouse model was selected to evaluate whether immunization onto bare skin can induce protective immune responses against lethal systemic challenge with LT.…”

Section: Discussionmentioning

confidence: 99%

The LTR72 Mutant of Heat-Labile Enterotoxin ofEscherichia coliEnhances the Ability of Peptide Antigens To Elicit CD4⁺T Cells and Secrete Gamma Interferon after Coapplication onto Bare Skin

et al. 2002

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Application of antigens with an adjuvant onto bare skin is a needle-free and pain-free immunization procedure that delivers antigens to the immunocompetent cells of the epidermis. We tested here the immunogenicity and adjuvanticity of two mutants of heat-labile enterotoxin (LT) of Escherichia coli, LTK63 and LTR72. Both mutants were shown to be immunogenic, inducing serum and mucosal antibody responses. The application of LTK63 and LTR72 to bare skin induced significant protection against intraperitoneal challenge with a lethal dose of LT. In addition, both LT mutants enhanced the capacity of peptides TT:830-843 and HA:307-319 (representing T-helper epitopes from tetanus toxin and influenza virus hemagglutinin, respectively) to elicit antigen-specific CD4 ؉ T cells after coapplication onto bare skin. However, only mutant LTR72 was capable of stimulating the secretion of high levels of gamma interferon. These findings demonstrate that successful skin immunization protocols require the selection of the right adjuvant in order to induce the appropriate type of antigen-specific immune responses in a selective and reliable way. Moreover, the use of adjuvants such the LTK63 and LTR72 mutants, with no or low residual toxicity, holds a lot of promise for the future application of vaccines to the bare skin of humans.Recently, bare skin has emerged as a potential alternative route for vaccine delivery (11,27). This is because the skin is rich in immunocompetent cells (4, 36), and when antigens are applied with a suitable adjuvant either in solution (1,11,13,34) or with a patch (14), they induce potent immune responses. The development of noninvasive immunization procedures, which can be needle free and pain free, is a top priority for public health agencies. This is because many current immunization practices are unsafe, particularly in developing countries due to the widespread reuse of nonsterile syringes (27). Therefore, the topical application of vaccines is attractive since it has the potential to make vaccine delivery more equitable, safer, and efficient. Furthermore, it would greatly facilitate the successful implementation of worldwide mass vaccination campaigns against infectious diseases.For the induction of an effective immune response, the antigen is normally coapplied onto hydrated bare skin with an ADP-ribosylating exotoxin as an adjuvant (i.e., Vibrio cholerae cholera toxin [CT] or Escherichia coli heat-labile enterotoxin [LT]) (1, 11, 13, 34). Both CT and LT are composed of five nontoxic B subunits held together in a pentamer (responsible for binding to the cell membrane), surrounding a single A subunit, which is responsible for toxicity. The A subunit consists of two distinct structural domains: the A1 domain, which displays the ADP-ribosyltransferase activity in the cytosol of the target cells and the A2 domain that interacts with the B-subunit (35). These toxins are responsible for the cause of a debilitating watery diarrhea (35). Moreover, they are potent immunogens and exert an adjuvant effect on ant...

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Mechanisms of resistance to S. mansoni infection: the rat model

Cited by 40 publications

References 36 publications

Cutting Edge: Susceptibility to the Larval Stage of the Helminth ParasiteTaenia crassicepsIs Mediated by Th2 Response Induced Via STAT6 Signaling

Cutting Edge: Susceptibility to the Larval Stage of the Helminth ParasiteTaenia crassicepsIs Mediated by Th2 Response Induced Via STAT6 Signaling

Cytokine Production in Whole Blood Cultures from a Fishing Community in an Area of High Endemicity forSchistosoma mansoniin Uganda: the Differential Effect of Parasite Worm and Egg Antigens

The LTR72 Mutant of Heat-Labile Enterotoxin ofEscherichia coliEnhances the Ability of Peptide Antigens To Elicit CD4⁺T Cells and Secrete Gamma Interferon after Coapplication onto Bare Skin

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Mechanisms of resistance to S. mansoni infection: the rat model

Cited by 40 publications

References 36 publications

Cutting Edge: Susceptibility to the Larval Stage of the Helminth ParasiteTaenia crassicepsIs Mediated by Th2 Response Induced Via STAT6 Signaling

Cutting Edge: Susceptibility to the Larval Stage of the Helminth ParasiteTaenia crassicepsIs Mediated by Th2 Response Induced Via STAT6 Signaling

Cytokine Production in Whole Blood Cultures from a Fishing Community in an Area of High Endemicity forSchistosoma mansoniin Uganda: the Differential Effect of Parasite Worm and Egg Antigens

The LTR72 Mutant of Heat-Labile Enterotoxin ofEscherichia coliEnhances the Ability of Peptide Antigens To Elicit CD4+T Cells and Secrete Gamma Interferon after Coapplication onto Bare Skin

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The LTR72 Mutant of Heat-Labile Enterotoxin ofEscherichia coliEnhances the Ability of Peptide Antigens To Elicit CD4⁺T Cells and Secrete Gamma Interferon after Coapplication onto Bare Skin