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immunologie@vetmed.fu-berlin.de
The domestic pig represents the ideal outbred model to study the immune responses against Ascaris, the most common of the soil-transmitted helminths. A. lumbricoides and A. suum infecting humans and pigs, are genetically highly similar and thus highlight the role of pig studies to understand host-parasite interactions. Following epithelial invasion, L3 larvae start a tissue migratory phase through liver and lung before establishing in the small intestine.
While chronic infection triggers a prototypical Th2 response locally in the small intestinal lamina propria, it is less clear where and in which form the parasite-specific CD4+ T cell response is initially instructed. We therefore performed a time-course study (0-8w p.i.) in experimentally single infected pigs to monitor induction and progression of the Ascaris-antigen-responding CD4+ T cell pool during primary infection - cells that are rare, but of upmost importance for orchestrating the anti-parasite defense program.
Circulating A. suum-specific T cells were identified based on CD40L expression upon antigen recognition and magnetic enrichment enabled their functional characterization in the periphery where they were found significantly increased in numbers after Ascaris L3 larvae had passed the lung (14 dpi). Parasite-specific T cells induced by larval migration demonstrated a strong IL-4 phenotype, mainly co-expressed with TNFa. While the phenotype of circulating parasite-specific T cells was stably maintained until chronic stage of infection, their numbers constantly increased until week 5 p.i. when adult worms establish in the gut. On an individual level, numbers of circulating, parasite-specific T cell positively correlated with the individual worm burden, arguing for increased antigen availability in high-level infected pigs. To more specifically address the lung tissue at an important induction site for Ascaris-antigen recognizing T cells, we studied tissue infiltrating specific T cells at day 7 p.i (beginning of lung stage) and day 12 p.i. (final lung stage). Only at 12 dpi we were able to detect lung infiltrating parasite-specific cells that interestingly showed an increased level of IFNg compared to circulating T cells. This indicates that tissue destruction during migration locally shapes the phenotype of the Ascaris-specific T cell response.