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Published on: November 27, 2014
MyD88-dependent pathways mediate resistance to Cryptosporidium parvum infection in mice
K A Rogers1, A B Rogers, B A Leav
1Division of Geographic Medicine and Infectious Diseases, Tufts-New England Medical Center, 750 Washington Street, Boston, MA 02111, USA.
Abstract:
Cryptosporidium spp. cause diarrheal disease worldwide. Innate immune responses mediating resistance to this parasite are not completely understood. To determine whether MyD88-dependent pathways play a role in resistance to Cryptosporidium parvum, we compared the course of infection in MyD88(-/-) mice to that in their wild-type (WT) littermate controls. Three- to 4-week-old mice were infected with C. parvum, and infection was monitored by quantifying fecal oocyst shedding. Twelve days postinfection, the histology of the intestines was examined to quantify intestinal parasite burden and to determine if there were any pathological changes. Fecal oocyst shedding and intestinal parasite burden were significantly greater in MyD88(-/-) mice than in littermate controls. Nonetheless, both WT and MyD88(-/-) mice cleared the infection within 3 weeks. These results indicate that MyD88-dependent pathways are involved in mediating initial resistance to C. parvum. Since gamma interferon (IFN-gamma) is known to mediate resistance to C. parvum, we also studied infection in MyD88(-/-) mice and WT controls in which this cytokine was temporarily neutralized. Fecal oocyst shedding, as well as intestinal parasite burden, intestinal inflammation, and mortality, was significantly greater in MyD88(-/-) mice in which IFN-gamma was neutralized than in IFN-gamma-neutralized WT mice or in MyD88(-/-) mice in which this cytokine was active. These results suggest that MyD88 and IFN-gamma had an additive effect in conferring protection from C. parvum infection. While this study confirms the importance of IFN-gamma in conferring resistance to infection with C. parvum, it suggests that MyD88-mediated pathways also play a role in innate immunity to this parasite.
Insights
MyD88-dependent pathways are crucial for initial resistance against Cryptosporidium parvum infection in mice. This innate immunity pathway, alongside gamma interferon (IFN-γ), enhances protection against the parasite.
Area of Science:
- Immunology
- Infectious Diseases
- Microbiology
Background:
- Cryptosporidium spp. are significant global causes of diarrheal disease.
- The innate immune mechanisms conferring resistance to Cryptosporidium are not fully elucidated.
Purpose of the Study:
- To investigate the role of MyD88-dependent pathways in host resistance to Cryptosporidium parvum infection.
- To assess the interplay between MyD88 and gamma interferon (IFN-γ) in Cryptosporidium resistance.
Main Methods:
- Comparison of C. parvum infection course in MyD88(-/-) mice and wild-type (WT) littermate controls.
- Quantification of fecal oocyst shedding and intestinal parasite burden.
- Histological examination of intestinal tissues for pathological changes.
- Assessment of infection in MyD88(-/-) and WT mice with and without IFN-γ neutralization.
Main Results:
- MyD88(-/-) mice exhibited significantly higher fecal oocyst shedding and intestinal parasite burden compared to WT controls.
- Despite initial resistance differences, both MyD88(-/-) and WT mice cleared the infection within three weeks.
- Neutralization of IFN-γ exacerbated infection severity in MyD88(-/-) mice more than in WT controls, indicating an additive protective effect.
Conclusions:
- MyD88-dependent pathways are integral to the initial innate immune response against C. parvum.
- MyD88 and IFN-γ act additively to confer protection against C. parvum infection.
- These findings highlight MyD88-mediated pathways as a significant component of innate immunity against Cryptosporidium.
