Dynamics of mucosal and systemic Th2 / Th1 effector T cells in response to tissue migrating Ascaris suum infections

Abstract text

Introduction: The large roundworm Ascaris suum is one of the most relevant and frequent soil-transmitted helminths observed in pigs. Commonly, early infection and constant reinfection with A. suum can be observed. However, initial infection factors that may influence the development of efficient type 2 immune responses during larval migration are poorly understood. Here, we investigated the local and systemic adaptive immunity along the hepatotracheal migration route of Ascaris suum during primary infection in growing pigs.

Materials & methods: German-Landrace crossbreds were inoculated orally with a single dose of 4000 A. suum ova and dissected at different time points post before patent infection was established. Immunophenotyping for type 2 and 1 signatures was performed on PBMC and spleen and compared to local responses in nematode-migration affected tissues (liver, lung, small intestine, and their corresponding lymph nodes). In addition, Ascaris-specific CD4+ Th cells and their cytokine profile were assessed.

Results: Our initial data indicate that systemic Th2 levels remain constantly low during larval migration. Contrarily, we found local and transient Th2 responses in the lungs and lungLN, but not in the liver of infected animals after A. suum L3 had migrated through these tissues. The initial invasion of the small intestine did not elicit a type 2 response. However, Th2 cells accumulated locally with the return of larvae and their maturation into pre-adult worms. Interestingly, robust Th1 responses developed both in the circulation and in most of the investigated organs and draining lymph nodes. However, at all stages of infection, the majority of CD4+ T cells directly recognizing A. suum antigens produced high levels of IL-4. Meanwhile, parasite-specific IFN-g+ T cells were less frequently observed.

Conclusion: Our findings show that in growing pigs primary, experimental infection with A. suum does not induce a fulminant systemic type 2 response, but locally and kinetically restricted Th2 immunity. Because Th2 cells are known to orchestrate an efficient anti-parasite response, we propose that the ubiquitous and potentially infection-driven type 1 immune signature observed in conventionally raised pigs holds back the development of a strong type 2 response. Thus, further research is currently ongoing to evaluate if the weak type 2 immunity observed might contribute to susceptibility and constant reinfection observed in domestic pigs.