Immune responses to third stage larvae of Onchocerca volvulus in interferon-gamma and interleukin-4 knockout mice.
To shed clarity on the dichotomy of reported results relative to the significance of T helper-1 vs T helper-2 immune responses in onchocerciasis, we compared the survivability of Onchocerca volvulus third-stage larvae (L3) in immunized mice that had either a targeted disruption of the Interleukin-4 or Interferon-gamma gene. Treatment groups consisted of control mice and mice immunized with irradiated O. volvulus L3. All mice were challenged with diffusion chambers containing viable L3. Vaccinated IL-4-/- were unable to kill this larval target. In contrast, vaccinated INF-gamma-/- and C57BL/6 mice, exhibited high levels of killing, had elevated levels of IL-4 and significantly greater numbers of eosinophils in their diffusion chambers than the IL-4-/-. Whereas, levels of IFN-gamma in all three groups of immunized mice were equivalent to those of control mice, levels of IL-5 were elevated, even in the IL-4-/-, indicating that cytokines other than IL-4 were involved in its production. The protective immune response to third-stage larvae of O. volvulus in mice vaccinated with irradiated larvae has an absolute IL-4 requirement.
Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520-8016, USA.
E H
EH
Johnson
S
S
Schynder-Candrian
T V
TV
Rajan
F K
FK
Nelson
S
S
Lustigman
D
D
Abraham
D000818:Animals; D015194:Diffusion Chambers, Culture; D007114:Immunization; D007371:Interferon-gamma / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D015848:Interleukin-5 / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017181:Onchocerca volvulus / Q000276:immunology*; D009855:Onchocerciasis / Q000276:immunology*
D015848:Interleukin-5; D015847:Interleukin-4; D007371:Interferon-gamma