IL‐12 Knockout C57BL/6 Mice are Protected from Re‐infection with <i>Cryptosporidium parvum</i> after Challenge

Ehigiator, Humphrey N.; McNair, Nina; Mead, Jan R.

doi:10.1111/j.1550-7408.2003.tb00622.x

Cited by 17 publications

(14 citation statements)

References 18 publications

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“…Additionally for IL‐12KO mice, which were resistant to re‐challenge even 189 days p.i. (44), we showed that the specific antibody titres were already decreased to the baseline levels 14 weeks p.i.…”

Section: Discussionmentioning

confidence: 71%

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Humoral immune response in IL‐12 and IFN‐γ deficient mice after infection with Cryptosporidium parvum

Jakobi

Petry

2008

Parasite Immunology

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Infection with Cryptosporidium spp. causes diarrhoeal disease and has become an important medical and veterinary problem especially in the immunocompromised host. The importance of the adaptive immune response, with CD4+ T-lymphocytes being the major players, has been clearly demonstrated. The requirement of IL-12 and IFN-gamma identifies this response as a Th1-dominated reaction. IFN-gamma is also important in the early phase of the host-parasite interaction. We analysed the outcome of infection in IL-12p40 (IL-12KO) and IFN-gamma (GKO) deficient C57BL/6 mice after primary and secondary challenge with the parasite and, for the first time, we demonstrate the resulting Ig response in sera and vaginal lavages. Although showing differences in the extent and the time course both strains of mice were able to clear infection and developed an almost complete resistance to re-infection. While GKO mice mounted prolonged parasite-specific IgG and IgA responses after primary infection, in IL-12KO mice IgG and IgA titres dropped over time. Re-challenge of mice 5 weeks after primary infection led to a booster effect in Ig response despite the absence of oocyst shedding. The data from infection and re-challenge experiments suggest that in IL-12- or IFN-gamma-deficient mice the development of resistance involves other protective immune responses.

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Section: Discussionmentioning

confidence: 71%

“…unpublished data; cited in Ref. (44)), which demonstrates that sterile resistance does not occur. Our results suggest that survival is not dependent on IFN‐γ but this cytokine is necessary for parasite clearance.…”

Section: Discussionmentioning

confidence: 85%

Humoral immune response in IL‐12 and IFN‐γ deficient mice after infection with Cryptosporidium parvum

Jakobi

Petry

2008

Parasite Immunology

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“…The roles of proinflammatory cytokines have been extensively studied in C. parvum infection. Several studies have reported that IL-12 plays a critical role in the differentiation of Th1 cells and the subsequent production of IFN-γ, which is important for controlling C. parvum infection (Urban et al, 1996; Ehigiator et al, 2003; Pollock et al, 2001). TNF-α showed the highest upregulation among the cytokines studied (Fig.…”

Section: Resultsmentioning

confidence: 99%

Interaction ofCryptosporidium parvumwith mouse dendritic cells leads to their activation and parasite transportation to mesenteric lymph nodes

Pérez-Cordón

Yang²,

Zhou³

et al. 2013

Pathogens Disease

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Dendritic cells (DCs) are the antigen presenting cells capable of activating naïve T cells. Although CD4+ T cells are crucial for Cryptosporidium parvum clearance, little is known about the role of DCs in the immune response to this parasite. In this study the interaction between mouse DCs and C. parvum was investigated both in vitro and in vivo. For in vitro experiments, mouse bone marrow-derived dendritic cells (BMDCs) derived from wild type C57B1/6 or MyD88−/− or C3H/HeJ mice and DC cell line DC2.4 were pulsed with C. parvum. Active invasion of parasites was demonstrated by parasite co-localization with host cell membranes and actin-plaque formation at the site of attachment. DC activation induced by the parasite invasion was demonstrated by upregulation of costimulatory molecules CD40, CD80, and CD86, as well as inflammatory cytokines IL-12, TNF-α, and IL-6. BMDCs derived from MyD88−/− and C3H/HeJ mice failed to produce IL-12 in response to C. parvum, suggesting the importance of TLR-dependent signaling pathway specially presence of a functional TLR4 pathway, for C. parvum-induced cytokine production. In vivo experiments showed that both parasite antigens and live parasites were transported to mice mesenteric lymph nodes. All together, these data suggest that DCs play a key role in host immune responses to C. parvum and pathogenesis of the disease.

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“…Our laboratory developed a C57BL/6 IL-12KO mouse model to evaluate C. parvum infection (35). This model offers a number of qualities essential for immunological studies, such as high susceptibility, development of a mixed Th1/Th2 mucosal response, resolution of the infection, and protection from re-infection (29, 36).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of DNA encoding acidic ribosomal protein P2 of Cryptosporidium parvum as a potential vaccine candidate for cryptosporidiosis

Benitez

Priest

Ehigiator³

et al. 2011

Vaccine

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The Cryptosporidium parvum acidic ribosomal protein P2 (CpP2) is an important immunodominant marker in C. parvum infection. In this study, the CpP2 antigen was evaluated as a vaccine candidate using a DNA vaccine model in adult C57BL/6 IL-12 knockout (KO) mice, which are susceptible to C. parvum infection. Our data show that subcutaneous immunization in the ear with DNA encoding CpP2 (CpP2-DNA) cloned into the pUMVC4b vector induced a significant anti-CpP2 IgG antibody response that was predominantly of the IgG1 isotype. Compared to control KO mice immunized with plasmid alone, CpP2-immunized mice demonstrated specific in vitro spleen cell proliferation as well as enhanced IFN-γ production to recombinant CpP2. Further, parasite loads in CpP2 DNA-immunized mice were compared to control mice challenged with C. parvum oocysts. Although a trend in reduction of infection was observed in the CpP2 DNA-immunized mice, differences between groups were not statistically significant. These results suggest that a DNA vaccine encoding the C. parvum P2 antigen is able to provide an effective means of eliciting humoral and cellular responses and has the potential to generate protective immunity against C. parvum infection but may require using alternative vectors or adjuvant to generate a more potent and balanced response.

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IL‐12 Knockout C57BL/6 Mice are Protected from Re‐infection with Cryptosporidium parvum after Challenge

Cited by 17 publications

References 18 publications

Humoral immune response in IL‐12 and IFN‐γ deficient mice after infection with Cryptosporidium parvum

Humoral immune response in IL‐12 and IFN‐γ deficient mice after infection with Cryptosporidium parvum

Interaction ofCryptosporidium parvumwith mouse dendritic cells leads to their activation and parasite transportation to mesenteric lymph nodes

Evaluation of DNA encoding acidic ribosomal protein P2 of Cryptosporidium parvum as a potential vaccine candidate for cryptosporidiosis

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