Immune response to chronic <i>Toxocara canis</i> infection in a mice model

Helminths do often invade the central nervous system (CNS) of vertebrates, including humans, causing severe pathologies, such as in the case of neurocysticercosis (NCC) or neurotoxocarosis. 1 Although the CNS was formerly considered an immune-privileged site with a limited capacity to develop an adaptive immune response, this view has recently been revisited. 2,3 Inflammatory cells are recruited into the infected CNS as well as pathogen-specific T cells, which were primed in the periphery. 4 The polarization of helminth-specific T helper (Th) cells largely orchestrates the host immune response. Th1 and Th17 populations are usually associated with host pathology, contrary to Th2 response and expansion of regulatory T cells (Treg) which suggest asymptomatic or mild infection. 5 For example, symptomatic NCC is linked to increased serum levels of proinflammatory cytokines 6 while Th2/ Treg milieu is related to asymptomatic NCC. 6-9 However, it is not very clear how the host immune response is influenced by the cysts present directly in the CNS and those disseminated in other body parts. The same applies to Toxocara spp. which exhibits a marked Abstract Trichobilharzia regenti (Schistosomatidae) percutaneously infects birds and mammals and invades their central nervous system (CNS). Here, we characterized the peripheral immune response of infected mice and showed how it was influenced by the parasite-induced inflammation in the skin and the CNS. As revealed by flow cytometry, T cells expanded in the spleen and the CNS-draining lymph nodes 7-14 days post-infection. Both T-bet+ and GATA-3+ T cells were markedly elevated suggesting a mixed type 1/2 immune response. However, it dropped after 7 dpi most likely being unaffected by the neuroinflammation. Splenocytes from infected mice produced a high amount of IFN-γ and, to a lesser extent, IL-10, IL-4 and IL-17 after in vitro stimulation by cercarial homogenate. Nevertheless, it had only a limited capacity to alter the maturation status of bone marrow-derived dendritic cells (BMDCs), contrary to the recombinant T. regenti cathepsin B2, which also strongly augmented expression of Ccl5, Cxcl10, Il12a, Il33 and Il10 by BMDCs. Taken together, mice infected with T. regenti developed the mixed type 1/2 immune response, which was driven by the early skin inflammation rather than the late neuroinflammation. Parasite peptidases might play an active role in triggering the host immune response. K E Y W O R D S cathepsin B, central nervous system, dendritic cells, lymph nodes, skin, spleen, T lymphocytes

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“…The same applies to Toxocara spp. which exhibits a marked affinity towards the CNS but most larvae are still localized in muscle tissue 10,11 …”

Section: Introductionmentioning

confidence: 99%

The peripheral immune response of mice infected with a neuropathogenic schistosome

Majer

Macháček

Súkeníková

et al. 2020

Parasite Immunology

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“…Furthermore, the expansion of CD4 + FoxP3 + T cells in lymphoid organs of mice with chronic T. canis infection, along with the higher levels of IL-10 in spleen and sera, support their role in the host systemic regulatory response to the infection [82]. The occurrence of Treg cells was observed in both the spleen and peripheral lymph nodes, where CD4 + FoxP3 + , as well as CD8 + FoxP3 + cells, were increased [82]. The anti-inflammatory role of Tregs has been confirmed in experimental infections with Trichinella spiralis, where suppression of gut inflammation was related to the increased expression of IL-10 and TGF-β and expansion of Tregs [83].…”

Section: Discussionmentioning

confidence: 77%

“…The infection of mice with T. canis is apparently associated with alternatively activated macrophages (AAMs), which have anti-inflammatory functions [81]. Furthermore, the expansion of CD4 + FoxP3 + T cells in lymphoid organs of mice with chronic T. canis infection, along with the higher levels of IL-10 in spleen and sera, support their role in the host systemic regulatory response to the infection [82]. The occurrence of Treg cells was observed in both the spleen and peripheral lymph nodes, where CD4 + FoxP3 + , as well as CD8 + FoxP3 + cells, were increased [82].…”

Section: Discussionmentioning

confidence: 99%

Infection with Toxocara canis Inhibits the Production of IgE Antibodies to α-Gal in Humans: Towards a Conceptual Framework of the Hygiene Hypothesis?

et al. 2020

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α-Gal syndrome (AGS) is a type of anaphylactic reaction to mammalian meat characterized by an immunoglobulin (Ig)E immune response to the oligosaccharide α-Gal (Galα1-3Galβ1-4GlcNAc-R). Tick bites seems to be a prerequisite for the onset of the allergic disease in humans, but the implication of non-tick parasites in α-Gal sensitization has also been deliberated. In the present study, we therefore evaluated the capacity of helminths (Toxocara canis, Ascaris suum, Schistosoma mansoni), protozoa (Toxoplasma gondii), and parasitic fungi (Aspergillus fumigatus) to induce an immune response to α-Gal. For this, different developmental stages of the infectious agents were tested for the presence of α-Gal. Next, the potential correlation between immune responses to α-Gal and the parasite infections was investigated by testing sera collected from patients with AGS and those infected with the parasites. Our results showed that S. mansoni and A. fumigatus produce the terminal α-Gal moieties, but they were not able to induce the production of specific antibodies. By contrast, T. canis, A. suum and T. gondii lack the α-Gal epitope. Furthermore, the patients with T. canis infection had significantly decreased anti-α-Gal IgE levels when compared to the healthy controls, suggesting the potential role of this nematode parasite in suppressing the allergic response to the glycan molecule. This rather intriguing observation is discussed in the context of the ‘hygiene hypothesis’. Taken together, our study provides new insights into the relationships between immune responses to α-Gal and parasitic infections. However, further investigations should be undertaken to identify T. canis components with potent immunomodulatory properties and to assess their potential to be used in immunotherapy and control of AGS.

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“…The host immune response is induced by the T. canis larvae excretory-secretory (TES) products, and the evasion of this response allows the nematode to survive for many years in different host tissues (18). The mouse immune response to T. canis chronic infection has been reported as a type 2 response and a regulatory one (28). This is characterized by an increased proportion of F4/80 + macrophages, CD19 + lymphocytes, and CD4 + Foxp3 + Treg cells in the spleen, as well as higher splenic and serum levels of IL-4, IL-10, and VEGF (28).…”

Section: Introductionmentioning

confidence: 99%

“…The mouse immune response to T. canis chronic infection has been reported as a type 2 response and a regulatory one (28). This is characterized by an increased proportion of F4/80 + macrophages, CD19 + lymphocytes, and CD4 + Foxp3 + Treg cells in the spleen, as well as higher splenic and serum levels of IL-4, IL-10, and VEGF (28). For the abovementioned reasons, T. canis could regulate the host immune response, and in turn, favor tumor growth (29).…”

Section: Introductionmentioning

confidence: 99%

Potential Novel Risk Factor for Breast Cancer: Toxocara canis Infection Increases Tumor Size Due to Modulation of the Tumor Immune Microenvironment

et al. 2020

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Worldwide, breast cancer is the most important type of cancer in women with regard to incidence and prevalence. Several risk factors interact to increase the probability of breast cancer development. Biological environmental contaminants such as infectious agents play a significant role in tumor development, and helminths have been recognized as cancer enhancers or inducers due to their ability to regulate the host immune response. Toxocara canis is a zoonotic and cosmopolite nematode with immuno-regulatory abilities. T. canis infection has been related to T helper type-2 cell (Th2 or type 2) and regulatory responses. Type 2 and regulatory immune responses may favor the development of comorbidities that are usually controlled or eliminated through a type 1 response such as cancer. The aim of this study was to determine whether T. canis infection alters mammary tumor growth through modulation of the immune response. Infected mice developed larger tumors. Tumor immune cell milieu analysis revealed that infection reduced the proportions of CD8 + lymphocytes and increased the proportions of F4/80 + macrophages and CD19 + B cells. These changes were accompanied by a type 2 local response represented by increased amounts of IL-4 and VEGF and a regulatory microenvironment associated with higher IL-10 levels. Thus, this study demonstrates that T. canis infection enhances tumor development and suggests that this is through modulation of the tumor immune microenvironment.

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Immune response to chronic Toxocara canis infection in a mice model

Cited by 21 publications

References 39 publications

The peripheral immune response of mice infected with a neuropathogenic schistosome

The peripheral immune response of mice infected with a neuropathogenic schistosome

Infection with Toxocara canis Inhibits the Production of IgE Antibodies to α-Gal in Humans: Towards a Conceptual Framework of the Hygiene Hypothesis?

Potential Novel Risk Factor for Breast Cancer: Toxocara canis Infection Increases Tumor Size Due to Modulation of the Tumor Immune Microenvironment

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