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Published on: March 12, 2015
Characterization of experimental Cryptosporidium parvum infection in IFN-gamma knockout mice
1Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Abstract:
Severe cryptosporidial infections were produced in gamma interferon (IFN-gamma) knockout mice. Mean oocyst shedding increased from 332 to 30,717 oocysts/100 microliters of faecal suspension between day 4 and 9 after administration of 1 x 10(5) oocysts/mouse. No significant differences in oocyst shedding were observed in mice after being inoculated with 1 x 10(5), 1 x 10(4) or 1 x 10(3) oocysts/mouse (P > 0.05). Infected mouse weights decreased an average 3-4 g before death or euthanization. Histological studies revealed heavy parasite colonization in small intestinal epithelium (approximately 250 organisms/high-power field at x 400). Mesenteric lymph nodes in infected mice were markedly enlarged compared to controls (P < 0.05). Both CD4+ and CD8+ T cell populations increased in spleens of infected mice while the B cell population increased in mesenteric lymph nodes from infected mice. No significant proliferation was observed when pooled lymphocytes from infected mice were exposed to C. parvum antigens in vitro. Addition of recombinant mouse IFN-gamma did not restore antigen responsiveness. While lymphoproliferative responses to specific antigen were not significant in the short period following infection, this mouse model provides unique features to study the characteristics of acute infection and the immune response against C. parvum.
Insights
Severe cryptosporidial infections cause significant oocyst shedding and weight loss in gamma interferon (IFN-γ) knockout mice. This model reveals intestinal parasite colonization and altered immune cell populations during acute infection.
Area of Science:
- Immunology
- Infectious Diseases
- Parasitology
Background:
- Cryptosporidiosis is a significant cause of diarrheal disease, particularly in immunocompromised individuals.
- Gamma interferon (IFN-γ) plays a crucial role in controlling intracellular parasitic infections.
Purpose of the Study:
- To investigate the role of IFN-γ in controlling Cryptosporidium parvum infection using a knockout mouse model.
- To characterize the host immune response during acute cryptosporidiosis.
Main Methods:
- Generation of severe cryptosporidial infections in IFN-γ knockout mice.
- Quantification of oocyst shedding and monitoring of host weight.
- Histological analysis of intestinal tissues and immune cell profiling (CD4+, CD8+, B cells) in spleen and mesenteric lymph nodes.
- In vitro assessment of lymphocyte proliferation in response to C. parvum antigens.
Main Results:
- IFN-γ knockout mice exhibited severe cryptosporidiosis with high oocyst shedding and significant weight loss.
- Heavy parasite colonization was observed in the small intestinal epithelium.
- Enlarged mesenteric lymph nodes and increased CD4+, CD8+ T cells in spleen and B cells in lymph nodes were noted.
- No significant lymphoproliferative response to C. parvum antigens was detected in vitro, even with added IFN-γ.
Conclusions:
- The absence of IFN-γ leads to severe, uncontrolled C. parvum infection in mice.
- The observed immune cell changes suggest a complex host response during acute infection.
- This IFN-γ knockout mouse model is valuable for studying acute cryptosporidiosis and host-parasite interactions.
