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

Resende NM, Gazzinelli-Guimarães PH, Barbosa FS, Oliveira LM, Nogueira DS, Gazzinelli-Guimarães AC, Gonçalves MT, Amorim CC, Oliveira FM, Caliari MV, Rachid MA, Volpato GT, Bueno LL, Geiger SM, Fujiwara RT - Parasit Vectors (2015)

Bottom Line: Nematodes of the genus Toxocara are cosmopolitan roundworms frequently found in dogs and cats.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.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. nathy_resende@yahoo.com.br.

ABSTRACT

Background: Nematodes 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.

Methods: Parasitological 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.

Results: We 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.

Conclusion: In 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.

No MeSH data available.


Related in: MedlinePlus

Liver parenchyma of Toxocara canis-infected BALB/c mice. a Control group: normal liver parenchyma with H&E staining. Bar = 100 μm. b 7 days post-infection (p.i.): inflammatory infiltration (arrowheads) and small area of hepatic necrosis (*). H&E. Bar = 100 μm. c 14 days p.i.: area with intense inflammatory infiltration (arrowheads) and hepatic necrosis (*). H&E. Bar = 100 μm. d 14 days p.i.: higher magnification of the previous figure showing inflammatory infiltrate consisting of eosinophils (arrowheads) and neutrophils (arrows), as well as necrosis (*). H&E. Bar = 50 μm
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Fig3: Liver parenchyma of Toxocara canis-infected BALB/c mice. a Control group: normal liver parenchyma with H&E staining. Bar = 100 μm. b 7 days post-infection (p.i.): inflammatory infiltration (arrowheads) and small area of hepatic necrosis (*). H&E. Bar = 100 μm. c 14 days p.i.: area with intense inflammatory infiltration (arrowheads) and hepatic necrosis (*). H&E. Bar = 100 μm. d 14 days p.i.: higher magnification of the previous figure showing inflammatory infiltrate consisting of eosinophils (arrowheads) and neutrophils (arrows), as well as necrosis (*). H&E. Bar = 50 μm

Mentions: The histopathological evaluation of the livers of uninfected animals showed a normal histological appearance, with the hepatic tissue formed by the lobular vein center surrounded by cords of hepatocytes and sinusoidal capillaries. The hepatocytes presented with a polygonal shape and central spherical nuclei (Fig. 3a). The livers from animals at 7 days p.i. showed regions with moderate focal inflammatory infiltrate, consisting primarily of eosinophils and neutrophils, and small regions were occasionally permeated with necrosis of hepatocytes and polymorphonuclear cell infiltration. Perivascular inflammatory infiltration was also observed (Fig. 3b). The livers of animals at 14 days p.i. showed lesions in the hepatic parenchyma, characterized by large areas with intense inflammatory infiltrates composed of neutrophils and eosinophils, as well as areas with moderate hepatic necrosis associated with polymorphonuclear inflammatory infiltrate. Intensive perivascular inflammatory infiltrates were also present (Fig. 3c and d). The lesion area of the liver was larger due to the duration of the infection (Fig. 4).Fig. 3


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

Resende NM, Gazzinelli-Guimarães PH, Barbosa FS, Oliveira LM, Nogueira DS, Gazzinelli-Guimarães AC, Gonçalves MT, Amorim CC, Oliveira FM, Caliari MV, Rachid MA, Volpato GT, Bueno LL, Geiger SM, Fujiwara RT - Parasit Vectors (2015)

Liver parenchyma of Toxocara canis-infected BALB/c mice. a Control group: normal liver parenchyma with H&E staining. Bar = 100 μm. b 7 days post-infection (p.i.): inflammatory infiltration (arrowheads) and small area of hepatic necrosis (*). H&E. Bar = 100 μm. c 14 days p.i.: area with intense inflammatory infiltration (arrowheads) and hepatic necrosis (*). H&E. Bar = 100 μm. d 14 days p.i.: higher magnification of the previous figure showing inflammatory infiltrate consisting of eosinophils (arrowheads) and neutrophils (arrows), as well as necrosis (*). H&E. Bar = 50 μm
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4494798&req=5

Fig3: Liver parenchyma of Toxocara canis-infected BALB/c mice. a Control group: normal liver parenchyma with H&E staining. Bar = 100 μm. b 7 days post-infection (p.i.): inflammatory infiltration (arrowheads) and small area of hepatic necrosis (*). H&E. Bar = 100 μm. c 14 days p.i.: area with intense inflammatory infiltration (arrowheads) and hepatic necrosis (*). H&E. Bar = 100 μm. d 14 days p.i.: higher magnification of the previous figure showing inflammatory infiltrate consisting of eosinophils (arrowheads) and neutrophils (arrows), as well as necrosis (*). H&E. Bar = 50 μm
Mentions: The histopathological evaluation of the livers of uninfected animals showed a normal histological appearance, with the hepatic tissue formed by the lobular vein center surrounded by cords of hepatocytes and sinusoidal capillaries. The hepatocytes presented with a polygonal shape and central spherical nuclei (Fig. 3a). The livers from animals at 7 days p.i. showed regions with moderate focal inflammatory infiltrate, consisting primarily of eosinophils and neutrophils, and small regions were occasionally permeated with necrosis of hepatocytes and polymorphonuclear cell infiltration. Perivascular inflammatory infiltration was also observed (Fig. 3b). The livers of animals at 14 days p.i. showed lesions in the hepatic parenchyma, characterized by large areas with intense inflammatory infiltrates composed of neutrophils and eosinophils, as well as areas with moderate hepatic necrosis associated with polymorphonuclear inflammatory infiltrate. Intensive perivascular inflammatory infiltrates were also present (Fig. 3c and d). The lesion area of the liver was larger due to the duration of the infection (Fig. 4).Fig. 3

Bottom Line: Nematodes of the genus Toxocara are cosmopolitan roundworms frequently found in dogs and cats.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.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. nathy_resende@yahoo.com.br.

ABSTRACT

Background: Nematodes 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.

Methods: Parasitological 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.

Results: We 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.

Conclusion: In 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.

No MeSH data available.


Related in: MedlinePlus