<i>Cryptosporidium parvum</i>-Specific CD4 Th1 Cells from Sensitized Donors Responding to Both Fractionated and Recombinant Antigenic Proteins

Morales, María Ángeles Gómez; Mele, Rita; Ludovisi, Alessandra; Bruschi, Fabrizio; Tosini, Fabio; Pozio, Edoardo

doi:10.1128/iai.72.3.1306-1310.2004

Cited by 27 publications

(15 citation statements)

References 44 publications

(42 reference statements)

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“…Indeed, clearance of C. parvum infection in mice requires CD4+ T-cell production of IFNγ (Ungar et al, 1991; Wyatt et al, 1997; Theodos 1998; McDonald et al, 2000; Gomez Morales et al, 2004). The role of the proinflammatory cytokine TNFα during C. parvum infection is less clear.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“… 47 In humans, T-cell clones isolated from the blood of patients previously infected with Cryptosporidium and then stimulated with cryptosporidial antigen fractions or recombinant peptides ex-vivo are predominantly CD4 + CD45RO + memory cells. 48 These cells were found to be mainly α/β T cells and produced either IFN-γ alone or in combination with IL-4 or IL-5. In addition, challenge infection leads to an increase in immunoglobulin response in mice 49 and pre-existing antibodies was associated with less oocyst shedding in challenged human volunteers.…”

Section: Immune Responses Elicited By Cryptosporidium mentioning

confidence: 97%

Prospects for immunotherapy and vaccines againstCryptosporidium

Mead

2014

Human Vaccines & Immunotherapeutics

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Cryptosporidium spp is a ubiquitous parasite that has long been recognized as a frequent cause of protozoal diarrhea in humans. While infections in immunocompetent hosts are usually self-limiting, immunocompromised individuals can develop severe, chronic, and life-threatening illness. Vaccine development or immunotherapy that prevents disease or reduces the severity of infection is a relevant option since efficacious drug treatments are lacking. In particular, children in developing countries might benefit the most from a vaccine since cryptosporidiosis in early childhood has been reported to be associated with subsequent impairment in growth, physical fitness, and intellectual capacity. In this review, immunotherapies that have been used clinically are described as well as experimental vaccines and their evaluation in vivo.

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“…2 Lymphocytes from people who have recovered from cryptosporidiosis produce IFN␥ after antigen stimulation in vitro. 3,4 In volunteer studies, expression of IFN␥ was associated with resistance to infection and prior sensitization. 5 Thus, expression of IFN␥ is an important marker of immunity to infection.…”

mentioning

confidence: 99%

Seropositive Human Subjects Produce Interferon Gamma after Stimulation with Recombinant Cryptosporidium hominis gp15

et al. 2007

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Cryptosporidiosis is an important cause of diarrhea worldwide. In normal hosts, infection is self-limited and associated with seroconversion and partial immunity to reinfection. Immunity is associated with interferon gamma (IFNgamma) production. Cryptosporidium surface proteins gp15 and gp40 are among the immunodominant proteins in terms of antibody responses. We asked the question of whether these antigens also stimulate production of IFNgamma in patients who have serologic evidence of prior infection. Whole blood from seropositive donors was stimulated with recombinant gp15 and gp 40 from Cryptosporidium hominis and Cryptosporidium parvum or His-tag controls. C. hominis gp15 stimulated increased production of IFNgamma. By contrast, there was no significant increase after stimulation with C. parvum gp15 or either gp40 preparation. IFNgamma production in response to C. hominis gp15 was noted in both CD4(+) and CD8(+) cells. This highlights the potential for C. hominis gp15 as a vaccine candidate for human cryptosporidiosis.

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Cryptosporidium parvum-Specific CD4 Th1 Cells from Sensitized Donors Responding to Both Fractionated and Recombinant Antigenic Proteins

Cited by 27 publications

References 44 publications

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

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

Prospects for immunotherapy and vaccines againstCryptosporidium

Seropositive Human Subjects Produce Interferon Gamma after Stimulation with Recombinant Cryptosporidium hominis gp15

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