MyD88-Dependent Pathways Mediate Resistance toCryptosporidium parvumInfection in Mice
| Autor: | Kathleen A. Rogers, Shizuo Akira, Brett A. Leav, Arlin B. Rogers, Ana M. Sanchez, Edouard Vannier, Honorine D. Ward, Douglas T. Golenbock, Satoshi Uematsu |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
Ratón animal diseases medicine.medical_treatment Immunology Cryptosporidiosis Intestinal parasite Biology medicine.disease_cause Microbiology Interferon-gamma Mice Immunity parasitic diseases medicine Animals Parasite hosting Interferon gamma Receptors Immunologic Adaptor Proteins Signal Transducing Cryptosporidium parvum Mice Knockout Innate immune system Enterocolitis biology.organism_classification Antigens Differentiation Immunity Innate Mice Inbred C57BL Infectious Diseases Cytokine Myeloid Differentiation Factor 88 Female Parasitology Fungal and Parasitic Infections Signal Transduction medicine.drug |
| Zdroj: | Infection and Immunity. 74:549-556 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.74.1.549-556.2006 |
| Popis: | Cryptosporidiumspp. 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 toCryptosporidium 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 withC. 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 toC. parvum. Since gamma interferon (IFN-γ) is known to mediate resistance toC. 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-γ was neutralized than in IFN-γ-neutralized WT mice or in MyD88−/−mice in which this cytokine was active. These results suggest that MyD88 and IFN-γ had an additive effect in conferring protection fromC. parvuminfection. While this study confirms the importance of IFN-γ in conferring resistance to infection withC. parvum, it suggests that MyD88-mediated pathways also play a role in innate immunity to this parasite. |
| Databáze: | OpenAIRE |
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