Blood–brain barrier dysfunction occurring in mice infected with Angiostrongylus cantonensis

Lee, June-Der; Tsai, Li-Yu; Chen, Chun-Hsiang; Wang, Jhi-Joung; Hsiao, Jen-Kuei; Yen, Chuan-Min

doi:10.1016/j.actatropica.2005.11.003

Cited by 44 publications

(42 citation statements)

References 34 publications

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“…Generally, pathogens may cross the BBB trancellularly, paracellularly, and/or by means of infected phagocytes (for a review see Katchanov and Nawa 2010). Similarly, as for Angiostrongylus (Lee et al 2006), it can be supposed that Toxocara spp. can cross BBB trans-or paracellularly.…”

Section: Discussionmentioning

confidence: 98%

“…can cross BBB trans-or paracellularly. The BBB impairment is frequently associated with leukocytosis due to meningitis caused by various microbial agents (Stibbs and Curtis 1987, Lee et al 2006, Brown et al 2000. Although T. canis larvae could invade the area surrounding the plexus chorioideus, they did not elicit inflammatory cell infiltration or cerebral parenchymal injury in the brain (Epe et al 1994, Fan et al 2003, Liao et al 2008.…”

Section: Discussionmentioning

confidence: 99%

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Toxocara canis larvae reinfecting BALB/c mice exhibit accelerated speed of migration to the host CNS

et al. 2011

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Using a small animal imaging system, migratory activity of Toxocara canis larvae stained by carboxyfluorescein succinimidyl ester (CFSE) was observed post primary infection (PPI) and post reinfection (PR) of BALB/c mice. Each infection was performed with 1,000 larvae per mouse. Primary infections were performed with labeled larvae, while for challenge infections the reinfecting larvae were stained by CFSE. The worm burden in mouse organs was determined during a period from 6 h to 21 days and 4 months PPI and PR. In comparison with primary infections that led to the first larvae appearance in the brain after 60 h, greatly accelerated migration of the parasites administered 3 weeks PPI to the CNS and eyes of challenged mice was noted-in both organs the larvae appeared 6 h PR. In all challenged mice, reinfecting larvae prevailed in the resident parasite population. Preliminary experiments with Toxocara cati larvae also revealed early brain involvement in primarily infected mice. Staining of T. canis larvae by CFSE had no effect on the development of a humoral antibody response against T. canis excretory-secretory antigens. In ELISA, elevated levels of specific IgG and IgG1 were noted on day 14 PPI and the levels of antibodies increased till the end of experiment. Reinfection induced an increase in the levels of both antibodies. In terms of optical density, IgG1 antibodies gave higher values in all sera examined. In ELISA for IgG antibodies, an increase in the avidity index of around 50% was detected 1 month PPI; higher-avidity antibodies were also detected in sera of reinfected animals.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Toxocara canis larvae reinfecting BALB/c mice exhibit accelerated speed of migration to the host CNS

et al. 2011

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“…The larvae then penetrate the intestinal wall and migrate to the central nervous system where they develop into L4 and L5, causing eosinophilic meningitis or meningoencephalitis accompanied with dysfunction of the blood-brain barrier in non-permissive hosts (Tsai et al 2008;Lee et al 2006). But in permissive hosts, L5 could migrate to and settle in the pulmonary arteries where they develop into adult worms (Alicata 1965).…”

Section: Discussionmentioning

confidence: 97%

Molecular cloning and characterization of a cathepsin B from Angiostrongylus cantonensis

Han

et al. 2011

Parasitol Res

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Cysteine proteases, a superfamily of hydrolytic enzymes, have numerous functions in parasites. Here, we reported the cloning and characterization of a cDNA encoding a cathepsin B (AcCPB) from Angiostrongylus cantonensis fourth-stage larvae cDNA library. The deduced amino acid sequence analysis indicated AcCPB is related to other cathepsin B family members with an overall conserved architecture. AcCPB is evolutionarily more close to other parasitic nematode cathepsin B than the ones from hosts, sharing 43-53% similarities to the homologues from other organisms. Real-time quantitative PCR analysis revealed that AcCPB was expressed significantly higher in the fourth-stage larvae (L4) and the fifth-stage larvae (L5) than that in the third-stage larvae (L3) and adult worms (Aw). Unexpectedly, AcCPB was expressed at a higher level in L4 and L5 derived from mice than the larvae at the same stages derived from rats. The protease activity of recombinant AcCPB (rAcCPB) expressed in Escherichia coli showed high thermostability and acidic pH optima. The role in ovalbumin digestion and enzyme activity of rAcCPB could be evidently inhibited by cystatin from A.cantonensis. Furthermore, we found rAcCPB increased the expression levels of CD40, MHC II, and CD80 on LPS-stimulated dendritic cells (DCs). In this study, we provided the first experimental evidence for the expression of cathepsin B in A.cantonensis. Besides its highly specific expression in the stages of L4 and L5 when the worms cause dysfunction of the blood-brain barrier of hosts, AcCPB displayed different expression profiles in non-permissive host- and permissive host-derived larval stages and was involved in the maturation of DCs, suggesting a potential role in the central nervous system invasion and the immunoregulation during parasite-host interactions.

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“…Rats serve as the definitive host of the nematode. However, when nonpermissive hosts such as humans and mice are infected with this parasite, the worms are carried by the blood to the brain where they develop into young adults but fail to reach maturity (Tsai et al 2008;Lee et al 2006). Human angiostrongyliasis occurs predominantly in tropical and subtropical regions (Hwang and Chen 1991;Wang et al 2002;Slom and Johnson 2003;Raccurt et al 2003;Alto 2001;Tsai et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Cloning and characterization of a novel cathepsin B-like cysteine proteinase from Angiostrongylus cantonensis

Cheng

Xiao²,

Li³

et al. 2012

Parasitol Res

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Cysteine protease plays a key role in host-parasite interactions. In this study, we identified a novel gene encoding a cathepsin B-like cysteine protease (AcCBL1) from the cDNA library of Angiostrongysus cantonensis fourth-stage larvae (L4) and characterized its biological role in the parasite. Sequence and phylogeny analysis showed that AcCBL1 is related to other cathepsin B family members with the conserved catalytic triad (Cys, His, Asn) and diagnostic occluding loop. In addition, the sequence contains a specific "hemoglobinase motif" and might have a hemoglobinase (Hb)-degrading function. The recombinant AcCBL1 (rAcCBL1) exhibited the protease activity by gelation SDS/PAGE assay; rAcCBL1 can cleave the fluorogenic substrate Z-Arg-Arg-AMC, and the optimum pH was 5.5. The enzyme can hydrolyse several host proteins including Hb and human IgG in acidic pH, but low levels of hydrolysis were observed in neutral pH. Reverse transcription polymerase chain reaction revealed that AcCBL1 expression was detected throughout various developmental stages, L3, L4, adult male and female worms. Western blotting analysis indicated that AcCBL1 was an excretory/secretory product of L4 in mature form of protease. Immunolocalization demonstrated that AcCBL1 was mainly localized in the intestine of L4. These results suggest that rAcCBL1 may play an important role in the parasite nutrition uptake.

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Blood–brain barrier dysfunction occurring in mice infected with Angiostrongylus cantonensis

Cited by 44 publications

References 34 publications

Toxocara canis larvae reinfecting BALB/c mice exhibit accelerated speed of migration to the host CNS

Toxocara canis larvae reinfecting BALB/c mice exhibit accelerated speed of migration to the host CNS

Molecular cloning and characterization of a cathepsin B from Angiostrongylus cantonensis

Cloning and characterization of a novel cathepsin B-like cysteine proteinase from Angiostrongylus cantonensis

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