Cryptosporidium parvum: The contribution of Th1-inducing pathways to the resolution of infection in mice

• Published in: Experimental parasitology 2007-02, Vol.115 (2), p.107-113
• Main Authors: Ehigiator, Humphrey N., McNair, Nina, Mead, Jan R.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cryptosporidiosis - immunology; Cryptosporidium parvum; Cryptosporidium parvum - immunology; Female; Fundamental and applied biological sciences. Psychology; Host resistance; IL-12p40-knockout; Interferon (IFN)-γ; Interferon-gamma - genetics; Interferon-gamma - immunology; Interleukin (IL)-18; Interleukin-12 - genetics; Interleukin-12 - immunology; Interleukin-18 - genetics; Interleukin-18 - immunology; Interleukin-23 - genetics; Interleukin-23 - immunology; Life cycle. Host-agent relationship. Pathogenesis; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Mouse; Oocyst; Protozoa; Stat1; STAT1 Transcription Factor - genetics; STAT1 Transcription Factor - immunology; Th1 Cells - immunology
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2006.07.001

The contribution of cytokines IL-12, IL-18, IL-23, and IFN-γ, 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-γ. 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.