Determination of the role of cytokines using gene deficient mice in African trypanosomiasis infection

African trypanosomiasis encompasses diseases caused by pathogenic trypanosomes, infecting both humans and animals alike. To determine the immunological role of IL=12 family members in Trypanosoma brucei brucei, Trypanosoma evansi and Trypanosoma congolense infections, IL-12p35¯/¯, IL-12p40¯/¯ and IL-12p35¯/¯/p40¯/¯ mice were used. While the two latter mouse strains lack all IL-12 homologues, IL-12p35¯/¯ mice still produce IL-12p80 homodimers and IL-23. In infection with T.b. brucei and T.evansi; IL-12p35¯/¯, IL-12p40¯/¯ or IL-12p35¯/¯/p40¯/¯ mice were susceptible to both these pathogens, demonstrated by increased mortality compared to wild type C57BL/6 mice. The different IL-12 deficient mouse strains showed similar mortality kinetics, suggesting that IL-12p70 but not the IL-12p80 homodimer or IL-23 plays a crucial role in survival. Similarly, parasitemia control was reduced in the absence of IL-12p70. While plasma levels of IgM and IgG2c were similar between IL-12 deficient mice and wild type mice, IF-γ production. As IFN-γR¯/¯ mice were also highly susceptible to both T.b. brucei and T. evansi, IL-12p70-dependent IFN-γ production seems to be important mechanism involved in resistance against both these pathogens.

Grantor dc:publisher.institution

Division of Immunology

Year dc:date.issued

2008

Author dc:creator

• Barkhuizen, Mark

Advisors dc:contributor.advisor

• Brombacher, Frank
• Magez, Sefan

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/11427/3119

OAI identifier oai:identifier

oai:open.uct.ac.za:11427/3119