Organ-specific Toxocara canis larvae migration and host immune response in experimentally infected mice

Abstract

We investigated organ specific <i>Toxocara canis</i> larval migration in mice infected with <i>T. canis</i> larvae. We observed the worm burden and systemic immune responses. Three groups of BALB/c mice (<i>n</i>=5 each) were orally administered 1,000 <i>T. canis</i> 2nd stage larvae to induce larva migrans. Mice were sacrificed at 1, 3, and 5 weeks post-infection. Liver, lung, brain, and eye tissues were collected. Tissue from 2 mice per group was digested for larval count, while the remaining 3 mice underwent histological analysis. Blood hematology and serology were evaluated and compared to that in a control uninfected group (<i>n</i>=5) to assess the immune response. Cytokine levels in bronchoalveolar lavage (BAL) fluid were also analyzed. We found that, 1 week post-infection, the mean parasite load in the liver (72±7.1), brain (31±4.2), lungs (20±5.7), and eyes (2±0) peaked and stayed constant until the 3 weeks. By 5-week post-infection, the worm burden in the liver and lungs significantly decreased to 10±4.2 and 9±5.7, respectively, while they remained relatively stable in the brain and eyes (18±4.2 and 1±0, respectively). Interestingly, ocular larvae resided in all retinal layers, without notable inflammation in outer retina. Mice infected with <i>T. canis</i> exhibited elevated levels of neutrophils, monocytes, eosinophils, and immunoglobulin E. At 5 weeks post-infection, interleukin (IL)-5 and IL-13 levels were elevated in BAL fluid. Whereas IL-4, IL-10, IL-17, and interferon-γ levels in BAL fluid were similar to that in controls. Our findings demonstrate that a small portion of <i>T. canis</i> larvae migrate to the eyes and brain within the first week of infection. Minimal tissue inflammation was observed, probably due to increase of anti-inflammatory cytokines. This study contributes to our understanding of the histological and immunological responses to <i>T. canis</i> infection in mice, which may have implications to further understand human toxocariasis.