Cryptosporidium parvum: the contribution of Th1-inducing pathways to the resolution of infection in mice.
The contribution of cytokines IL-12, IL-18, IL-23, and IFN-gamma, and Stat1 signaling molecules involved in Th1 responses associated with host resistance to Cryptosporidium parvum infection was investigated in adult IL-12p40(-/-)mice. Host resistance to C. parvum infection was assessed in different mouse strains lacking IL-12, IL-18, and IL-23 genes. We found that as in IL-12p40(-/-) mice (which lack both IL-12 and IL-23), IL-12p35(-/-) mice (which lack IL-12) and IL-18 deficient mice were also susceptible to infection with C. parvum. Varied levels of resistance were observed when mice were treated with cytokines like IL-18, IL-23 and IFN-gamma. Mice treated with IL-12, as expected, were completely resistant to infection until day 5 post infection, and had significantly decreased (85%) parasite loads at peak infection (day 7), whereas rIL-23 had a lesser effect, decreasing parasite load by approximately 45%. Interestingly, IL-18 appears to play a significant role in initial immune response, even in the absence of IL-12, since treatment with IL-18 in IL-12p40(-/-) knockout mice decreased parasite load by approximately 70%. In addition, the establishment of C. parvum infection in mice lacking the Stat1 gene demonstrated the involvement of this pathway in resolution of infection. These observations indicate a strong requirement for Th1 response in the development of immunity to C. parvum in the adult IL-12p40(-/-) mice, information that will be essential to further investigate the immune responses during infections and in the development of potential vaccine candidates.
Ehigiator
Humphrey N
HN
Veterans Affairs Medical Center, Medical Research 151, 1670 Clairmont Road, Decatur, GA 30033, USA.
McNair
Nina
N
Mead
Jan R
JR
D000818:Animals; D003457:Cryptosporidiosis / Q000276:immunology*; D016785:Cryptosporidium parvum / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology; D053759:Interleukin-23 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
D020382:Interleukin-18; D053759:Interleukin-23; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D018664:Interleukin-12; D007371:Interferon-gamma