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Infection and Immunity, November 2009, p. 5044-5049, Vol. 77, No. 11
0019-9567/09/$08.00+0     doi:10.1128/IAI.00377-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Roles for NK Cells and an NK Cell-Independent Source of Intestinal Gamma Interferon for Innate Immunity to Cryptosporidium parvum Infection{triangledown}

Farah M. Barakat,1 Vincent McDonald,1* James P. Di Santo,2 and Daniel S. Korbel1

Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Institute of Cell and Molecular Science, Centre for Gastroenterology, London, United Kingdom,1 Cytokines and Lymphoid Development Unit, Immunology Department, Institut Pasteur, Paris, France2

Received 3 April 2009/ Returned for modification 29 May 2009/ Accepted 10 August 2009

A gamma interferon (IFN-{gamma})-dependent innate immune response operates against the intestinal parasite Cryptosporidium parvum in T- and B-cell-deficient SCID mice. Although NK cells are a major source of IFN-{gamma} in innate immunity, their protective role against C. parvum has been unclear. The role of NK cells in innate immunity was investigated using Rag2–/– mice, which lack T and B cells, and Rag2–/– {gamma}c–/– mice, which, in addition, lack NK cells. Adult mice of both knockout lines developed progressive chronic infections; however, on most days the level of oocyst excretion was higher in Rag2–/– {gamma}c–/– mice and these animals developed morbidity and died, whereas within the same period the Rag2–/– mice appeared healthy. Neonatal mice of both mouse lines survived a rapid onset of infection that reached a higher intensity in Rag2–/– {gamma}c–/– mice. Significantly, similar levels of intestinal IFN-{gamma} mRNA were expressed in Rag2–/– and Rag2–/– {gamma}c–/– mice. Also, infections in each mouse line were exacerbated by treatment with anti-IFN-{gamma} neutralizing antibodies. These results support a protective role for NK cells and IFN-{gamma} in innate immunity against C. parvum. In addition, the study implies that an intestinal cell type other than NK cells may be an important source of IFN-{gamma} during infection and that NK cells may have an IFN-{gamma}-independent protective role.


* Corresponding author. Mailing address: Centre for Gastroenterology, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AT, United Kingdom. Phone: 44 020 7882 7201. Fax: 44 020 7882 2187. E-mail: v.mcdonald{at}qmul.ac.uk

{triangledown} Published ahead of print on 17 August 2009.

Editor: J. F. Urban, Jr.


Infection and Immunity, November 2009, p. 5044-5049, Vol. 77, No. 11
0019-9567/09/$08.00+0     doi:10.1128/IAI.00377-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.