New insights into the immunopathology of early Toxocara canis infection in mice

Abstract

BackgroundNematodes of the genus Toxocara are cosmopolitan roundworms frequently found in dogs and cats. Toxocara spp. can accidentally infect humans and cause a zoonosis called human toxocariasis, which is characterized by visceral, ocular or cerebral migration of larval stages of the parasite, without completing its life cycle. In general, chronic nematode infections induce a polarized TH2 immune response. However, during the initial phase of infection, a strong pro-inflammatory response is part of the immunological profile and might determine the outcome and/or pathology of the infection.MethodsParasitological aspects and histopathology during larval migration were evaluated after early T. canis experimental infection of BALB/c mice, which were inoculated via the intra-gastric route with a single dose of 1000 fully embryonated eggs. Innate immune responses and systemic cytokine patterns (TH1, TH2, TH17 and regulatory cytokines) were determined at different times after experimental challenge by sandwich ELISA.ResultsWe found that experimental infection with T. canis induced a mix of innate inflammatory/TH17/TH2 responses during early infection, with a predominance of the latter. The TH2 response was evidenced by significant increases in cytokines such as IL-4, IL-5, IL-13 and IL-33, in addition to increasing levels of IL-6 and IL-17. No significant increases were observed for IL-10, TNF-α or IFN-γ levels. In parallel, parasitological analysis clearly revealed the pattern of larval migration through the mouse organs, starting from the liver in the first 24 h of infection, reaching the peak in the lungs on the 3rd day of infection and finally being found numerously in the brain after 5 days of infection. Peripheral leukocytosis, characterized by early neutrophilia and subsequent eosinophilia, was remarkable during early infection. The tissue damage induced by larvae was evidenced by histopathological analysis of the organs at different time points of infection. In all of the affected organs, larval migration induced intense inflammatory infiltrate and hemorrhage.ConclusionIn conclusion, these new insights into early T. canis infection in mice presented here enabled a better understanding of the immunopathological events that might also occur during human toxocariasis, thus contributing to future strategies of diagnosis and control.

Immune response to chronic Toxocara canis infection in a mice model

“…Therefore, the immune balance among Th1, Th2 and their regulation is important for host survival and is different among parasites . As mentioned before, T canis infection induces both a type 2 and regulatory response but decreases type 1 cytokine production . Type 2 response was suggested in this study, associated with the augmentation of IL‐4 and the increased amount of serum IL‐5, in contrast to the reduction in type 1 response represented by diminished TNF‐α levels in spleen.…”

“…The migration of T canis larval throughout different tissues, as well as its establishment and immune response, depends on the paratenic host species, the number of larvated eggs administrated and the d.p.i . In this sense, BALB/c mice have proven to be a highly susceptible mice strain in that larval migrate to the brain as early as the 3 d.p.i., the majority of the larval are established in the brain and musculature, and no death related to the infection has been reported . To study the systemic chronic phase of the infection, 49 d.p.i.…”

“…Also, in T canis ‐infected mice, IL‐5 and IL‐4 levels were increased at 7 and 14 days post‐inoculation (d.p.i. ), respectively . Additionally, in human peripheral T cells specific for TES, IL‐4 and IL‐5 production was induced when cells were exposed to TES …”

“…The immune response to chronic T canis infection in paratenic hosts is associated with peripheral blood eosinophilia, eosinophilic infiltration around larval sites of migration, specific antibody production (IgG and IgE) and a T helper type 2 (Th2) response . This Th2 response has been demonstrated through serum cytokine detection and in vitro assays.…”

Cytokine Profile in Aqueous Humor of Patients with Ocular Toxocariasis

“…Despite OT being a well-known disease, intraocular host response and concrete mechanisms remain largely unknown. OT is believed to be derived from the intraocular immune response to the presence of Toxocara larvae and their products 6,7 . Cytokines play an important role in the coordination of the immune response, and their changing pro le may unravel the underlying mechanism.…”