Protection against the early acute phase of Cryptosporidium parvum infection conferred by interleukin-4-induced expression of T helper 1 cytokines.
Immunity to Cryptosporidium parvum infection involves a T helper (Th) 1 response with interferon (IFN)- gamma and interleukin (IL)-12 activity, but the role of Th2 cytokines, such as IL-4, is unclear. Around the peak of infection, production of oocysts in IL-4-deficient and IL-4 receptor alpha -deficient neonatal BALB/c mice was greater than that in wild-type (wt) mice. Susceptibility to infection was increased or decreased, respectively, in wt mice treated with anti-IL-4 neutralizing antibodies or recombinant IL-4. Excretion of oocysts by IFN- gamma -deficient mice was unaffected by treatment with anti-IL-4, indicating that IL-4 stimulated IFN- gamma activity. Early during infection, wt mice had increased intestinal expression of IFN- gamma and IL-12 mRNA, compared with IL-4-deficient mice. Intestinal IL-4 was detected by Western blotting in wt mice 24 h after infection but not in uninfected control mice. These findings suggest that, early during C. parvum infection of BALB/c mice, there is production of IL-4 that promotes Th1-mediated immunity.
Department of Adult and Paediatric Gastroenterology, Digestive Diseases Research Centre, Barts and the London School of Medicine, United Kingdom.
Stuart A C
SA
McDonald
John E
JE
O'Grady
Mona
M
Bajaj-Elliott
Clare A
CA
Notley
James
J
Alexander
Frank
F
Brombacher
Vincent
V
McDonald
D000208:Acute Disease; D000818:Animals; D000831:Animals, Newborn; D003457:Cryptosporidiosis / Q000276:immunology* / Q000469:parasitology; D016785:Cryptosporidium parvum / Q000276:immunology / Q000472:pathogenicity*; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D007422:Intestines / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D019948:Receptors, Interleukin-4 / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*
D016207:Cytokines; D012333:RNA, Messenger; D019948:Receptors, Interleukin-4; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma