Chronicity in Strongyloides stercoralis Infections: Dichotomy of the Protective Immune Response to Infective and Autoinfective Larvae in a Mouse Model

Strongyloidiasis is an intestinal disease that can last for decades due to the occurrence of autoinfective larvae (L3a) in an infected person, which contribute to the maintenance of the population of adult worms in the intestine. The goal of the present study was to determine if L3a are susceptible to the protective immunity that targets the infective stage of the worm, the third-stage larvae (L3). Mice immunized and challenged with Strongyloides stercoralis L3 kill more than 90% of challenge larvae contained within diffusion chambers. The L3 do not remain antigenically static in mice, however, but undergo some degree of antigenic change before they are killed, becoming host-activated larvae (L3+). The L3/L3+ are killed in this model system by the combined effects of both parasite-specific IgM and eosinophils. Mice immunized with L3 were able to kill L3/L3+, but did not kill L3a, in challenge infections. Eosinophils were, however, present in diffusion chambers containing L3a, and IgM bound to the surface of L3a. We hypothesized that differential IgM recognition of soluble L3a, L3, and L3+ antigens is the reason why the immune response generated against L3 could not kill L3a. Many common antigens on L3, L3+, and L3a were recognized by serum from mice immunized with L3, as determined by immunoblotting. However, several unique L3, L3+, and L3a antigens were also recognized by immune serum, thus indicating that antigen recognition with IgM antibodies is different between the L3, L3+, and L3a stages. This difference in antigen recognition could explain why L3a are able to evade the immune response that targets L3/L3+ in chronically infected hosts.