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Infection and Immunity, October 2006, p. 5497-5505, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00153-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Neutrophils Do Not Mediate the Pathophysiological Sequelae of Cryptosporidium parvum Infection in Neonatal Piglets

Leah M. Zadrozny,1 Stephen H. Stauffer,1 Martha U. Armstrong,1 Samuel L. Jones,2 and Jody L. Gookin1*

Departments of Molecular Biomedical Sciences,1 Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, North Carolina 276062

Received 30 January 2006/ Returned for modification 7 March 2006/ Accepted 3 July 2006

Cryptosporidium parvum is a minimally invasive protozoal pathogen of intestinal epithelium that results in villus atrophy, mucosal lipid peroxidation, diarrhea, and diminished barrier function. Influx of neutrophils is a consistent feature of human and animal cryptosporidiosis, and yet their contribution to the pathological sequelae of infection has not been investigated. Accordingly, we used an established neonatal piglet model of C. parvum infection to examine the role of neutrophils in disease pathogenesis by inhibiting their recruitment and activation in vivo using a monoclonal anti-CD18 antibody. Infected piglets were treated daily with anti-CD18 or isotype control immunoglobulin G and euthanized at peak infection, at which time neutrophil infiltrates, lipid peroxidation, severity of infection, and intestinal barrier function were quantified. C. parvum infection resulted in a significant increase in mucosal neutrophil myeloperoxidase activity that was prevented by treatment of piglets with anti-CD18 antibody. Neutrophil recruitment was dependent on mucosal superoxide formation (prevented by treatment of infected piglets with superoxide dismutase). Neutrophils did not contribute to peroxynitrite formation or peroxidative injury of C. parvum-infected mucosa and had no impact on the severity of epithelial infection, villus atrophy, or diarrhea. The presence of neutrophils in C. parvum-infected mucosa was associated with enhanced barrier function that could not be attributed to mucosal elaboration of prostaglandins or stimulation of their synthesis. These studies are the first to demonstrate that neutrophilic inflammation arising in response to infection by a noninvasive epithelial pathogen results in physiologic rather than pathological effects in vivo.

* Corresponding author. Mailing address: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606. Phone: (919) 513-6295. Fax: (919) 513-6465. E-mail: Jody_Gookin{at}ncsu.edu.

Editor: J. F. Urban, Jr.

Infection and Immunity, October 2006, p. 5497-5505, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00153-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





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