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IL-4- and IL-5-dependent protective immunity to Onchocerca volvulus infective larvae in BALB/cBYJ mice
A M Lange1, W Yutanawiboonchai, P Scott
1Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107.
Abstract:
A significant reduction in challenge worm survival occurred when BALB/cBYJ mice were vaccinated against Onchocerca volvulus infective third stage larvae (L3) by using irradiated O. volvulus L3. Challenge infections consisted of L3 implanted in diffusion chambers, which were used as a means to contain, and thus efficiently recover, the larvae from the host. The goal of the present study was to describe the mechanism of immune-mediated killing of O. volvulus L3 in diffusion chambers in mice. Direct contact between host cells and parasites was required for killing of larvae in immunized hosts. To define the mechanism of immune-mediated killing in this system, the time of influx of cells and cytokines into the infection site was compared with the time challenge infections were killed. The only cell type that was found to increase in diffusion chambers in immunized mice was eosinophils; maximal levels of eosinophils were coincident with the time of parasite killing. IL-5 was found in diffusion chambers of immunized mice coincident with the time of parasite killing; IL-5 was not found in diffusion chambers recovered from control mice. Significant levels of IFN-gamma were absent in the diffusion chambers of both groups. Immunized mice were treated with mAb to eliminate IL-5 or IL-4 to assess the role these cytokines or their by-products play in larval killing. Elimination of either IL-5 or IL-4 significantly reduced the protective effects of vaccination against larval O. volvulus.
Insights
Vaccination with irradiated Onchocerca volvulus larvae (L3) significantly reduced worm survival in mice. Immune cells, particularly eosinophils and IL-5, were crucial for this parasite killing mechanism.
Area of Science:
- Immunology
- Parasitology
- Molecular Biology
Background:
- Onchocerca volvulus (O. volvulus) infection poses a significant global health challenge.
- Vaccination strategies using irradiated infective third stage larvae (L3) have shown promise in reducing worm survival.
- The precise immune mechanisms underlying this protective effect require further elucidation.
Purpose of the Study:
- To investigate the cellular and molecular mechanisms of immune-mediated killing of O. volvulus L3 in a murine model.
- To determine the role of specific immune cells and cytokines in the vaccine-induced protection against O. volvulus challenge.
Main Methods:
- BALB/cBYJ mice were vaccinated with irradiated O. volvulus L3.
- Challenge infections were established using O. volvulus L3 within diffusion chambers implanted in mice.
- Cellular influx and cytokine profiles within diffusion chambers were analyzed over time.
- Monoclonal antibodies (mAbs) were used to deplete IL-5 and IL-4 to assess their roles.
Main Results:
- Direct contact between host cells and parasites was necessary for larval killing in immunized mice.
- Eosinophil infiltration into diffusion chambers correlated with parasite killing.
- Interleukin-5 (IL-5) was detected in diffusion chambers during parasite killing, while Interferon-gamma (IFN-gamma) was absent.
- Depletion of IL-5 or IL-4 significantly diminished the protective effects of vaccination.
Conclusions:
- Immune-mediated killing of O. volvulus L3 in vaccinated mice requires direct host cell contact.
- Eosinophils and the cytokine IL-5 play critical roles in the vaccine-induced immunity against O. volvulus.
- These findings highlight potential targets for developing more effective vaccines against onchocerciasis.