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Infection and Immunity, January 2006, p. 549-556, Vol. 74, No. 1
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.1.549-556.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

MyD88-Dependent Pathways Mediate Resistance to Cryptosporidium parvum Infection in Mice

Division of Geographic Medicine and Infectious Diseases, Tufts-New England Medical Center, 750 Washington Street, Boston, Massachusetts 02111,¹ Division of Comparative Medicine, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139,² Department of Host Defense, Research Institute for Microbial Diseases, Osaka University 3-1, Yamada-oka, Suita, Osaka 565-0871, Japan,³ Departments of Medicine, Infectious Diseases, and Immunology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655⁴

Received 15 June 2005/ Returned for modification 18 July 2005/ Accepted 9 October 2005

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-) 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- was neutralized than in IFN--neutralized WT mice or in MyD88^–/– mice in which this cytokine was active. These results suggest that MyD88 and IFN- had an additive effect in conferring protection from C. parvum infection. While this study confirms the importance of IFN- in conferring resistance to infection with C. parvum, it suggests that MyD88-mediated pathways also play a role in innate immunity to this parasite.

Editor: W. A. Petri, Jr.