Protective immunity to larval Strongyloides stercoralis in a mouse model

Harris Laeb Rotman, Thomas Jefferson University

Abstract

Strongyloidiasis is a disease caused by the nematode Strongyloides stercoralis, and normally causes only mild gastrointestinal distress, but can cause death due to hyperinfection in immunocompromised individuals. A mouse model for the infective stage of S. stercoralis larvae (L3) was developed. S. stercoralis larvae lived for two weeks in immunocompetent BALB/c mice, but did not undergo further development. Immunodeficient SCID mice, however, allowed infective larvae to develop to adulthood. BALB/c mice were immunized against S. stercoralis larvae using live, heat-killed, or homogenized L3, and greater than 90% of challenge L3 were killed after immunization with 10,000 live L3. The mechanisms involved in immune-mediated killing of S. stercoralis larvae were analyzed; protective immunity in mice was dependent on IL-4, IL-5, and granulocytes, thus indicating that a Th-2-type immune response was necessary for immunity. Immune mice showed increased serum IgGl and IgM, and an infiltration of eosinophils in the blood and in the infection sites. Human eosinophil granule products were able to kill host-adapted larvae. IgM was the only isotype in immune serum that bound to the surface of L3, and was the only isotype that conferred protective immunity in passive serum transfer experiments. Complement was also found to be essential in protective immunity, and additionally played a role in eosinophil infiltration into the microenvironment of the parasites. IL-12 was able to shift the immune response from a Th-2 to a Th-1-type response, and this ablated protective immunity to L3. This loss in protection was associated with a decrease in eosinophils, but did not affect IgM or complement levels. This study helps in defining the mechanisms involved in protective immunity in mice and will aid in vaccine development against S. stercoralis infection.

Subject Area

Immunology|Microbiology

Recommended Citation

Rotman, Harris Laeb, "Protective immunity to larval Strongyloides stercoralis in a mouse model" (1996). ETD Collection for Thomas Jefferson University. AAI9625294.
https://jdc.jefferson.edu/dissertations/AAI9625294

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