Cryptosporidium Parvum Biliary Tract Infection in Adult Immunocompetent and Immunosuppressed Mice

Verdon, Renaud; Polianski, J; Grodet, Alain; Garry, Louis; Carbon, C

doi:10.1099/00222615-47-1-71

Cited by 17 publications

(24 citation statements)

References 11 publications

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“…It is probable that the immunosuppressor effect of dexamethasone is dependent on the doses and the parasite because it has been shown that doses lower than 1 mg/kg/day provided immunosuppression in mice parasitised by protozoa (Verdon et al 1998;Kang et al 2006), although it did not provide the same effect in our study in mice infected by the nematode T. canis.…”

Section: Discussioncontrasting

confidence: 78%

“…The immunosuppressor effect of dexamethasone (5 mg/kg) observed in this study was also observed in other parasitoses, such as microsporidiosis caused by E. cuniculi in BALB/c strain mice (5 mg/kg) (Lallo et al 2002), the infection by Cryptosporidium parvum in the mice strains C57BL/6 and BALB/c (0.25 mg/kg/day) (Verdon et al 1998) and in the intensity of infection of Toxoplasma gondii in the brain (10 mg/l of water) in BALB/c strain mice (Kang et al 2006). It is probable that the immunosuppressor effect of dexamethasone is dependent on the doses and the parasite because it has been shown that doses lower than 1 mg/kg/day provided immunosuppression in mice parasitised by protozoa (Verdon et al 1998;Kang et al 2006), although it did not provide the same effect in our study in mice infected by the nematode T. canis.…”

Section: Discussionsupporting

confidence: 63%

“…In cryptosporidiosis and toxoplasmosis, both opportunistic parasitic infections, immunosuppression is a predisposing factor for increasing the intensity of the infection and worsening of the pathology (Verdon et al 1998;Kang et al 2006). However, in other parasitic zoonoses, such as toxocariasis, the influence of immunosuppression on the intensity of the infection is not completely understood.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the immunosuppressive effect of cyclophosphamide and dexamethasone in mice with visceral toxocariasis

et al. 2011

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Visceral toxocariasis is a serious public health problem with a cosmopolitan distribution. Children are susceptible due to their immature immune system and high risks of infection. Nevertheless, the few completed studies about immunosuppression have had controversial results. To evaluate the effect of two immunosuppressive drugs on the larval burden of Toxocara canis, four groups of ten Swiss strain mice each were inoculated on day 0 with 1,200 embryonated T. canis eggs. Fifteen days before the experimental infection, group 1 (control) was treated via intraperitoneal injection (IP) with sterile distilled water and groups 2 and 3 were treated with dexamethasone (DEX) at 1 and 5 mg/kg/day, respectively. Additionally, group 4 was treated IP with cyclophosphamide (CY) at 50 mg/kg at two times per week for 2 weeks. Sixty days following infection, the mice were euthanised to recover the larvae by means of the tissue digestion technique. The levels of antibodies detected by indirect ELISA were not associated with the larval burden. Administration of CY (50 mg/kg) and DEX (5 mg/kg) resulted in an increase of the larval burden of 162.1% and 50.8%, respectively, in relation to the control group. These two treatments, especially CY (50 mg/kg), promoted immunosuppression and the establishment of a significant larval burden, supporting its further utilisation in studies related to immunosuppression in visceral toxocariasis.

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Section: Discussioncontrasting

confidence: 78%

Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

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Evaluation of the immunosuppressive effect of cyclophosphamide and dexamethasone in mice with visceral toxocariasis

et al. 2011

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“…There are some benefits to this systemic exposure, as immunocompromised patients, especially HIV-positive individuals, may require exposures outside of the GI tract for therapy to be successful (Hunter and Nichols, 2002). Further studies on exposure to BKI 1369 in bile duct cannulated rats would be warranted since the biliary tract is a possible repository of infection in immunocompromised patients (Verdon et al, 1998). Inhibition of additional CYP enzymes by BKI 1369 should also be explored to avoid drug-to-drug interactions or effects on treatments for certain coinfections.…”

Section: Discussionmentioning

confidence: 99%

Advances in bumped kinase inhibitors for human and animal therapy for cryptosporidiosis

Hulverson

Choi

Arnold

et al. 2017

International Journal for Parasitology

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Improvements have been made to the safety and efficacy of bumped kinase inhibitors, and they are advancing toward human and animal use for treatment of cryptosporidiosis. As the understanding of bumped kinase inhibitor pharmacodynamics for cryptosporidiosis therapy has increased, it has become clear that better compounds for efficacy do not necessarily require substantial systemic exposure. We now have a bumped kinase inhibitor with reduced systemic exposure, acceptable safety parameters, and efficacy in both the mouse and newborn calf models of cryptosporidiosis. Potential cardiotoxicity is the limiting safety parameter to monitor for this bumped kinase inhibitor. This compound is a promising pre-clinical lead for cryptosporidiosis therapy in animals and humans.

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“…The protocol for infection and sacrifice of mice was approved by the Mayo Clinic Institutional Animal Care and Use Committee according to National Institute of Health guidelines. The in vivo induction of biliary cryptosporidiosis used in these mice was previously published (Verdon et al, 1998). Briefly, C. parvum oocysts were treated with a 10% bleach solution, washed twice with PBS, and injected directly into the gallbladder of 16 wild type C57BL and 16 TLR4 deficient mice through a small abdominal incision.…”

Section: Methodsmentioning

confidence: 99%

TLR4 Promotes Cryptosporidium parvum Clearance in a Mouse Model of Biliary Cryptosporidiosis

O’Hara

Bogert

Trussoni

et al. 2011

Journal of Parasitology

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Cholangiocytes, the epithelial cells lining intrahepatic bile ducts, express multiple toll-like receptors (TLRs) and thus have the capacity to recognize and respond to microbial pathogens. In previous work we demonstrated that TLR4, which is activated by gram-negative lipopolysaccharide (LPS), is upregulated in cholangiocytes in response to infection with Cryptosporidium parvum in vitro and contributes to NFkB activation. Here, using an in vivo model of biliary cryptosporidiosis we addressed the functional role of TLR4 in C. parvum infection dynamics and hepatobiliary pathophysiology. We observed that C57BL mice clear the infection by three weeks post-infection. In contrast, parasites were detected in bile and stool in TLR4 deficient mice at four weeks post-infection. The liver enzymes, alanine transaminase (ALT) and aspartate transaminase (AST), and the proinflammatory cytokines Tumor Necrosis Factor (TNF)-α, Interferon (IFN)-γ, and Interleukin (IL)-6 peaked at one to two weeks postinfection and normalized by four weeks in infected C57BL mice. C57BL mice also demonstrated increased cholangiocyte proliferation (PCNA staining) at one-week post-infection, which was resolved by two weeks post-infection. In contrast, TLR4 deficient mice showed persistently elevated serum ALT and AST, elevated hepatic IL-6 levels, and histological evidence of hepatocyte necrosis, increased inflammatory cell infiltration, and cholangiocyte proliferation through four weeks post-infection. These data suggest that a TLR4-mediated response is required for efficient eradication of biliary C. parvum infection in vivo, and lack of this pattern recognition receptor contributes to an altered inflammatory response and an increase in hepatobiliary pathology.

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Cryptosporidium Parvum Biliary Tract Infection in Adult Immunocompetent and Immunosuppressed Mice

Cited by 17 publications

References 11 publications

Evaluation of the immunosuppressive effect of cyclophosphamide and dexamethasone in mice with visceral toxocariasis

Evaluation of the immunosuppressive effect of cyclophosphamide and dexamethasone in mice with visceral toxocariasis

Advances in bumped kinase inhibitors for human and animal therapy for cryptosporidiosis

TLR4 Promotes Cryptosporidium parvum Clearance in a Mouse Model of Biliary Cryptosporidiosis

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