Immune Events Associated with High Level Protection against Schistosoma japonicum Infection in Pigs Immunized with UV-Attenuated Cercariae

Fang, Tian; Lin, Dan-Dan; Wu, Jingjiao; Gao, Yanan; Zhang, Donghui; Ji, Minjun; Wu, Guan-Ling

doi:10.1371/journal.pone.0013408

Cited by 33 publications

(28 citation statements)

References 41 publications

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“…One possible reason is that immune protection against schistosomes is associated with the induction of Th1-biased immune responses [30–32]. However, in our study, PD-1 blockade had no effect on Th1 immune responses.…”

Section: Discussioncontrasting

confidence: 69%

Blockade of PD-1 Signaling Enhances Th2 Cell Responses and Aggravates Liver Immunopathology in Mice with Schistosomiasis japonica

Zhou

Jin

et al. 2016

PLoS Negl Trop Dis

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BackgroundMore than 220 million people worldwide are chronically infected with schistosomes, causing severe disease or even death. The major pathological damage occurring in schistosomiasis is attributable to the granulomatous inflammatory response and liver fibrosis induced by schistosome eggs. The inflammatory response is tightly controlled and parallels immunosuppressive regulation, constantly maintaining immune homeostasis and limiting excessive immunopathologic damage in important host organs. It is well known that the activation of programmed death 1 (PD-1) signaling causes a significant suppression of T cell function. However, the roles of PD-1 signaling in modulating CD4+ T cell responses and immunopathology during schistosome infection, have yet to be defined.Methodology/Principal FindingsHere, we show that PD-1 is upregulated in CD4+ T cells in Schistosoma japonicum (S. japonicum)-infected patients. We also show the upregulation of PD-1 expression in CD4+ T cells in the spleens, mesenteric lymph nodes, and livers of mice with S. japonicum infection. Finally, we found that the blockade of PD-1 signaling enhanced CD4+ T helper 2 (Th2) cell responses and led to more severe liver immunopathology in mice with S. japonicum infection, without a reduction of egg production or deposition in the host liver.Conclusions/SignificanceOverall, our study suggests that PD-1 signaling is specifically induced to control Th2-associated inflammatory responses during schistosome infection and is beneficial to the development of PD-1-based control of liver immunopathology.

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Section: Discussioncontrasting

confidence: 69%

Blockade of PD-1 Signaling Enhances Th2 Cell Responses and Aggravates Liver Immunopathology in Mice with Schistosomiasis japonica

Zhou

Jin

et al. 2016

PLoS Negl Trop Dis

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“…In swine, IFN-γ has been shown to be related to IgG2 production [42] which supports the hypothesis that the IgG1:IgG2 ratio could provide a suitable indicator of adaptive immunity potentiation towards a Th1 or Th2 response, as in other species. Interestingly, our results showed that the post-challenge production of CSFV-specific IgG2, but not IgG1, was enhanced in vaccinated as compared to unvaccinated pigs.…”

Section: Discussionsupporting

confidence: 54%

CP7_E2alf oral vaccination confers partial protection against early classical swine fever virus challenge and interferes with pathogeny-related cytokine responses

Renson¹,

Dimna²,

Kéranflec’h³

et al. 2013

Vet Res

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The conventional C-strain vaccine induces early protection against classical swine fever (CSF), but infected animals cannot be distinguished from vaccinated animals. The CP7_E2alf marker vaccine, a pestivirus chimera, could be a suitable substitute for C-strain vaccine to control CSF outbreaks. In this study, single oral applications of CP7_E2alf and C-strain vaccines were compared for their efficacy to induce protection against a CSF virus (CSFV) challenge with the moderately virulent Bas-Rhin isolate, in pigs as early as two days post-immunization. This work emphasizes the powerful potential of CP7_E2alf vaccine administered orally by a rapid onset of partial protection similar to that induced by the C-strain vaccine. Furthermore, our results revealed that both vaccinations attenuated the effects induced by CSFV on production of the pig major acute phase protein (PigMAP), IFN-α, IL-12, IL-10, and TGF-β1 cytokines. By this interference, several cytokines that may play a role in the pathogeny induced by moderately virulent CSFV strains were revealed. New hypotheses concerning the role of each of these cytokines in CSFV pathogeny are discussed. Our results also show that oral vaccination with either vaccine (CP7_E2alf or C-strain) enhanced CSFV–specific IgG2 production, compared to infection alone. Interestingly, despite the similar antibody profiles displayed by both vaccines post-challenge, the production of CSFV-specific IgG1 and neutralizing antibodies without challenge was lower with CP7_E2alf vaccination than with C-strain vaccination, suggesting a slight difference in the balance of adaptive immune responses between these vaccines.

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“…With vaccines for schistosomes, the protection obtained with cercariae that have been attenuated with ionizing radiation is considered to be the ‘gold’ standard against which other vaccine candidates are compared for clinical development (McManus & Dalton, 2006; Hotez et al , 2008a; McManus & Loukas, 2008; Loukas et al , 2011). Elevated levels of protection against Schistosoma japonicum can be induced by exposure to X-irradiated cercariae in macaques (Hsu et al , 1969) and cattle (Hsu et al , 1983), by exposure to γ-irradiated cercariae in bovines (Hsu et al , 1984), and UV-attenuated cercariae in pigs (Tian et al , 2010). Vaccine efficacies are variable, however, as exemplified by immunization of mice with γ-irradiated cercariae of S. japonicum, which elicits only modest resistance to reinfection (Zhang et al , 1999).…”

Section: Discussionmentioning

confidence: 99%

Immunization and challenge shown by hamsters infected withOpisthorchis viverrinifollowing exposure to gamma-irradiated metacercariae of this carcinogenic liver fluke

et al. 2014

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Here we report findings to optimize and standardize conditions to attenuate metacercariae of Opisthorchis viverrini by ionizing radiation to elicit protective immune responses to challenge infection. Metacercariae were gamma-irradiated and the ability of irradiated metacercariae to prevent patent infection of challenge metacercariae in hamsters was determined, as well as their ability to induce a host antibody response. Metacercariae irradiated in a dose-dependent manner, with 3, 5, 10, 12, 20, 25 and 50 Gray, were used to infect Syrian golden hamsters by stomach gavage to ascertain the effect of irradiation on ability of the worms to establish infection. In addition, other hamsters were infected with metacercariae irradiated with 20–50 Gray, followed by challenge with intact/wild-type (non-irradiated) metacercariae to determine the protective effect as established by the numbers of adult flukes, eggs of O. viverrini in hamster faeces and anti-O. viverrini antibody titres. Significantly fewer worms were recovered from hamsters immunized with metacercariae irradiated at 20, 25 and 50 Gray than from control hamsters infected with intact metacercariae or 0 Gray, and the worms showed damaged reproductive organs. Faecal egg numbers were decreased significantly in hamsters immunized with 25 and 50 Gray metacercariae of O. viverrini. Moreover, hamsters administered metacercariae that were protected elicited a robust, specific anti-fluke immunoglobulin G response compared to control hamsters, suggesting a role for antibody in protection elicited by radiation-attenuated metacercariae.

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Immune Events Associated with High Level Protection against Schistosoma japonicum Infection in Pigs Immunized with UV-Attenuated Cercariae

Cited by 33 publications

References 41 publications

Blockade of PD-1 Signaling Enhances Th2 Cell Responses and Aggravates Liver Immunopathology in Mice with Schistosomiasis japonica

Blockade of PD-1 Signaling Enhances Th2 Cell Responses and Aggravates Liver Immunopathology in Mice with Schistosomiasis japonica

CP7_E2alf oral vaccination confers partial protection against early classical swine fever virus challenge and interferes with pathogeny-related cytokine responses

Immunization and challenge shown by hamsters infected withOpisthorchis viverrinifollowing exposure to gamma-irradiated metacercariae of this carcinogenic liver fluke

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