Abstract
Toxocariasis is a neglected disease that affects people around the world. Humans become infected by accidental ingestion of eggs containing Toxocara canis infective larvae, which upon reaching the intestine, hatch, penetrate the mucosa and migrate to various tissues such as liver, lungs and brain. Studies have indicated that Th2 response is the main immune defense mechanism against toxocariasis, however, there are still few studies related to this response, mainly the IL-33/ST2 pathway. Some studies have reported an increase in IL-33 during helminth infections, including T. canis. By binding to its ST2 receptor, IL-33 stimulating the Th2 polarized immune cell and cytokine responses. Thus, we aimed to investigate the role of the IL-33/ST2 pathway in the context of T. canis larval migration and the immunological and pathophysiological aspects of the infection in the liver, lungs and brain from Wild-Type (WT) BALB/c background and genetically deficient mice for the ST2 receptor (ST2-/-). The most important findings revealed that the IL-33/ST2 pathway is involved in eosinophilia, hepatic and cerebral parasitic burden, and induces the formation of granulomas related to tissue damage and pulmonary dysfunction. However, ST2-/- mice, the immune response was skewed to Th1/Th17 type than Th2, that enhanced the control of parasite burden related to IgG2a levels, tissue macrophages infiltration and reduced lung dysfunction. Collectively, our results demonstrate that the Th2 immune response triggered by IL-33/ST2 pathway mediates susceptibility to T. canis, related to parasitic burden, eosinophilia and granuloma formation in which consequently contributes to tissue inflammation and injury.
Highlights
Toxocariasis is a zoonosis caused by nematodes of the genus Toxocara, whose main etiologic agent is Toxocara canis [1,2], a neglected disease with cosmopolitan distribution worldwide and seroprevalence rates estimated at 19%
IL-33 is an alarmin that binds to the ST2 receptor, and some studies have observed an increase in this cytokine in toxocariasis, there are no studies regarding the IL-33/ ST2 role in this infection
Our results demonstrated that the IL-33/ST2 pathway is related to parasite burden on the liver and brain and increases the number of eosinophils in the blood and tissues
Summary
Toxocariasis is a zoonosis caused by nematodes of the genus Toxocara, whose main etiologic agent is Toxocara canis [1,2], a neglected disease with cosmopolitan distribution worldwide and seroprevalence rates estimated at 19%. The highest rates are associated with socioeconomic, geographic and environmental factors [3]. Humans are infected by accidental ingestion of T. canis eggs containing infective third stage larvae present in contaminated food, water, soil or utensils. The larvae penetrate the intestinal mucosa and migrate to multiple organs [4]. Human toxocariasis can manifest in different ways based on the parasite tropism, and the severity of the disease will depend on the parasitic burden, the duration of larval migration, aging and immunemediated responses of the immunocompromised individuals [2,5]. According to the larval migration site and clinical symptoms, toxocariasis is divided into four clinical forms: the Visceral larva migrans (VLM), Neurotoxocariasis (NT), Ocular toxocariasis (OT) and Covert or Common toxocariasis (CT) [2,4,5]
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