Roles for NK cells and an NK cell-independent source of intestinal gamma interferon for innate immunity to Cryptosporidium parvum infection.
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-/- gammac-/- 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-/- gammac-/- 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-/- gammac-/- mice. Significantly, similar levels of intestinal IFN-gamma mRNA were expressed in Rag2-/- and Rag2-/- gammac-/- 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.
Barakat
Farah M
FM
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.
McDonald
Vincent
V
Di Santo
James P
JP
Korbel
Daniel S
DS
D000818:Animals; D003457:Cryptosporidiosis / Q000276:immunology*; D016785:Cryptosporidium parvum / Q000276:immunology; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000276:immunology*; D007422:Intestines / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007371:Interferon-gamma
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