Role of cytokines in resistance to African trypanosomes
Date
1998-01-01
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
Type
Degree Level
Doctoral
Abstract
The early expression and role of cytokines in resistance to experimental Trypanosoma congolense infections in the highly susceptible BALB/c and relatively resistant C57BL/6 mice was studied. Higher levels of IL-4, IL-10 and IFN-γ were detected in the plasma of infected BALB/c than in C57BL/6 mice. In contrast, plasma levels of TNF-α were higher in C57BL/6 than in BALB/c mice. IL-10 and IFN-γ mRNA transcripts accumulated earlier and in higher concentrations in the spleens of susceptible than in resistant mice. TNF-α mRNA levels in the spleens were similar, but the hepatic TNF-α mRNA levels were higher in resistant than in susceptible mice on day 9. The kinetics of IL-4, IL-10 and IFN-γ spot-forming cells in the spleens were essentially similar but significantly higher numbers were detected in BALB/c than in C57BL/6 mice. In contrast, unstimulated and concanavalin A (Con A) stimulated splenocytes from BALB/c mice secreted high amounts of IL-4, IL-10 and IFN-γ in cultures starting from day 4. Secretion of IL-4 by splenocytes from infected C57BL/6 mice was undetectable throughout the period tested. Secretion of IL-10 and IFN-γ became appreciable on day 6 but were down regulated by day 8. Treatment of infected BALB/c mice with Berenil resulted in cure and caused a dramatic decline in the secretion of IL-10 and IFN-γ by BALB/c splenocytes. Con A-induced proliferation of splenocytes from infected BALB/c mice was progressively suppressed. Anti-IL-10 or anti-IFN-γ antibodies effectively reversed this suppression. Whereas in vivo administrations of anti-IL-10 antibodies to BALB/c mice early during infection only moderately prolonged their survival period, anti-IFN-γ antibodies shifted the phenotype of susceptible BALB/c mice to a resistant-like phenotype. Most of the IL-4, IL-10 and IFN-γ found in the infected BALB/c mice were produced by adherent Thy1.2⁻CD4⁻8⁻ splenocytes in synergy with adherent Thy1.2⁻ cells. These adherent cells suppressed T and B cell responses. Infected BALB/c mice mounted an earlier IgM response to various antigens of T. congolense than did C57BL/6 mice. In contrast, C57BL/6 mice made a strong and sustained IgG2a and IgG3 response to these antigens. It is hypothesized that resistance to T. congolense infection in mice is mediated by a TH1 cell response.
Description
Keywords
Citation
Degree
Doctor of Philosophy (Ph.D.)
Department
Veterinary Microbiology
Program
Veterinary Microbiology