Characteristics of Toxocara canis induced lung inflammation in C57BL/6 mice

Janina Lekki-Jóźwiak^1*Justyna Karabowicz²Magdalena Paschall²Karolina Gregorczyk- Zboroch²Małgorzata Sobczak-Filipiak³Piotr Bąska^2,4Irma Schabussova⁵Ewa Długosz²

• ¹Division of Parasitology and Invasiology, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland
• ²Institute of Veterinary Medicine, Department of Preclinical Sciences, Warsaw University of Life Sciences, Warsaw, Poland, Warsaw, Masovian, Poland
• ³Institute of Veterinary Medicine, Department of Pathology and Veterinary Diagnostics, Warsaw University of Life Sciences, Warsaw, Poland
• ⁴Laboratory of Parasitology, Military Institute of Hygiene and Epidemiology, Warsaw, Poland
• ⁵Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, Austria

Toxocariasis, a neglected zoonotic disease caused by parasites of the Toxocara genus, represents a significant public health concern, with an estimated global seroprevalence of 19%. Despite the well-known respiratory symptoms associated with toxocariasis, the immune response in the lungs during toxocariasis is still poorly understood. This study analyzes both local lung and systemic immune response to T. canis infection and T. canis excretory-secretory antigens (TES) intranasal application in C57BL/6J mice. Lungs, blood, and spleens were collected at specific time points for histopathological analyses, flow cytometry, cytokine profiling, and gene expression studies. The systemic immune response was further assessed by cytokine measurements in splenocyte cultures and the detection of TES-specific antibodies. T. canis infection triggered severe pulmonary inflammation characterized by eosinophilia and mucus accumulation, with persistent inflammation lasting up to 28 days post-infection. Interestingly, this response was not solely driven by Th2-type interleukin production. Cytokine analysis of splenocyte cultures revealed elevated levels of IL-5 and IL-6, along with increased TES-specific IgE and IgG1 antibody concentrations. In contrast, TES application alone induced local eosinophil infiltration and upregulated genes associated with lung repair, though this response was less intense and shorter-lived compared to the infection. Our study is the first to present a comprehensive cytokine proteome analysis in mouse lungs during T. canis infection and stimulation by larval antigens, highlighting the key role of cytokines such as IL-5, IL-6, and IL-33. These findings provide new insights into the pathogenesis of toxocariasis and underscore the need for further research into potential therapeutic targets.