Matrix metalloproteinase-9 leads to blood–brain barrier leakage in mice with eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis

Chiu, Ping-Sung; Lai, Shih‐Chan

doi:10.1016/j.actatropica.2014.08.015

Cited by 25 publications

(17 citation statements)

References 26 publications

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“…These are species in which blood represents the final microhabitat or a crucial migration road and most of them having an evident tropism for the central nervous system. Examples are nematodiasis such as angiostrongyliasis or eosinophilic meningoencephalitis (Chiu and Lai, 2014) and several protozooses such as cerebral malaria (Polimeni and Prato, 2014), trypanosomiasis including sleeping sickness and Chagas disease, leishmaniasis and toxoplasmic encephalitis in immunocompromised hosts (Geurts et al ., 2011). A mechanism by which parasite-derived products alter host expression of MMP and endogenous MMP inhibitors has only been described for hemozoin in malaria (Prato et al ., 2011).…”

Section: Discussionmentioning

confidence: 99%

NumerousFasciolaplasminogen-binding proteins may underlie blood-brain barrier leakage and explain neurological disorder complexity and heterogeneity in the acute and chronic phases of human fascioliasis

et al. 2018

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Human fascioliasis is a worldwide, pathogenic food-borne trematodiasis. Impressive clinical pictures comprising puzzling polymorphisms, manifestation multifocality, disease evolution changes, sequelae and mortality, have been reported in patients presenting with neurological, meningeal, neuropsychic and ocular disorders caused at distance by flukes infecting the liver. Proteomic and mass spectrometry analyses of theFasciola hepaticaexcretome/secretome identified numerous, several new, plasminogen-binding proteins enhancing plasmin generation. This may underlie blood-brain barrier leakage whether by many simultaneously migrating, small-sized juvenile flukes in the acute phase, or by breakage of encapsulating formations triggered by single worm tracks in the chronic phase. Blood-brain barrier leakages may subsequently occur due to a fibrinolytic system-dependent mechanism involving plasmin-dependent generation of the proinflammatory peptide bradykinin and activation of bradykinin B2 receptors, after different plasminogen-binding protein agglomeration waves. Interactions between diverse parasitic situations and non-imbalancing fibrinolysis system alterations are for the first time proposed that explain the complexity, heterogeneity and timely variations of neurological disorders. Additionally, inflammation and dilation of blood vessels may be due to contact system–dependent generation bradykinin. This baseline allows for search of indicators to detect neurological risk in fascioliasis patients and experimental work on antifibrinolytic treatments or B2 receptor antagonists for preventing blood-brain barrier leakage.

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Section: Discussionmentioning

confidence: 99%

NumerousFasciolaplasminogen-binding proteins may underlie blood-brain barrier leakage and explain neurological disorder complexity and heterogeneity in the acute and chronic phases of human fascioliasis

et al. 2018

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“…In AEM, MMP-9 expression increases, possibly due to the damage inflicted by migrating worms (Tsai et al 2008). Mouse studies of AEM suggest that eosinophils release MMP-9 into the subarachnoid space (Tseng et al 2004), activating a proteolytic cascade that disrupts the BBB (Chen et al 2006; Tsai et al 2008; Chiu and Lai, 2013, 2014). In mice with AEM, MMP-9 was also observed within endothelial cells lining the vascular spaces of the brain and in leucocytes within the subarachnoid space (Lai et al 2004).…”

Section: Pathophysiology and Clinical Manifestationsmentioning

confidence: 99%

Angiostrongylus cantonensis: a review of its distribution, molecular biology and clinical significance as a human pathogen

et al. 2016

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Angiostrongylus cantonensis is a metastrongyloid nematode found widely in the Asia-Pacific region, and the aetiological agent of angiostrongyliasis; a disease characterized by eosinophilic meningitis. Rattus rats are definitive hosts of A. cantonensis, while intermediate hosts include terrestrial and aquatic molluscs. Humans are dead-end hosts that usually become infected upon ingestion of infected molluscs. A presumptive diagnosis is often made based on clinical features, a history of mollusc consumption, eosinophilic pleocytosis in cerebral spinal fluid, and advanced imaging such as computed tomography. Serological tests are available for angiostrongyliasis, though many tests are still under development. While there is no treatment consensus, therapy often includes a combination of anthelmintics and corticosteroids. Angiostrongyliasis is relatively rare, but is often associated with morbidity and sometimes mortality. Recent reports suggest the parasites' range is increasing, leading to fatalities in regions previously considered Angiostrongylus-free, and sometimes, delayed diagnosis in newly invaded regions. Increased awareness of angiostrongyliasis would facilitate rapid diagnosis and improved clinical outcomes. This paper summarizes knowledge on the parasites' life cycle, clinical aspects and epidemiology. The molecular biology of Angiostrongylus spp. is also discussed. Attention is paid to the significance of angiostrongyliasis in Australia, given the recent severe cases reported from the Sydney region.

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“…However, detailed analysis of endothelial activation during A. vasorum infection in dogs is scarce. Interestingly, the closely related nematode Angiostrongylus cantonensis induces an increase in the blood–brain barrier via metalloproteinase 9 upregulation [ 45 ], thereby suggesting endothelial cell activation. In this context, related to the case of another heartworm that affect canids, D. immitis , it is well-known that its presence in the blood stream of the host causes endothelial cell activation and inflammation, a situation demonstrated in vivo and in vitro [ 46 ], situation attributed to progressive pulmonary endarteritis and muscular hypertrophy of arteriole walls [ 44 , 47 ].…”

Section: Introductionmentioning

confidence: 99%

Canine Angiostrongylus vasorum-Induced Early Innate Immune Reactions Based on NETs Formation and Canine Vascular Endothelial Cell Activation In Vitro

Grob

Conejeros

López-Osorio

et al. 2021

Biology

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Due to its localization in the canine blood stream, Angiostrongylus vasorum is exposed to circulating polymorphonuclear neutrophils (PMN) and the endothelial cells of vessels. NETs release of canine PMN exposed to A. vasorum infective stages (third stage larvae, L3) and early pro-inflammatory immune reactions of primary canine aortic endothelial cells (CAEC) stimulated with A. vasorum L3-derived soluble antigens (AvAg) were analyzed. Expression profiles of the pro-inflammatory adhesion molecules ICAM-1, VCAM-1, P-selectin and E-selectin were analyzed in AvAg-stimulated CAEC. Immunofluorescence analyses demonstrated that motile A. vasorum L3 triggered different NETs phenotypes, with spread NETs (sprNETs) as the most abundant. Scanning electron microscopy confirmed that the co-culture of canine PMN with A. vasorum L3 resulted in significant larval entanglement. Distinct inter-donor variations of P-selectin, E-selectin, ICAM-1 and VCAM-1 gene transcription and protein expression were observed in CAEC isolates which might contribute to the high individual variability of pathological findings in severe canine angiostrongylosis. Even though canine NETs did not result in larval killing, the entanglement of L3 might facilitate further leukocyte attraction to their surface. Since NETs have already been documented as involved in both thrombosis and endothelium damage events, we speculate that A. vasorum-triggered NETs might play a critical role in disease outcome in vivo.

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Matrix metalloproteinase-9 leads to blood–brain barrier leakage in mice with eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis

Cited by 25 publications

References 26 publications

NumerousFasciolaplasminogen-binding proteins may underlie blood-brain barrier leakage and explain neurological disorder complexity and heterogeneity in the acute and chronic phases of human fascioliasis

NumerousFasciolaplasminogen-binding proteins may underlie blood-brain barrier leakage and explain neurological disorder complexity and heterogeneity in the acute and chronic phases of human fascioliasis

Angiostrongylus cantonensis: a review of its distribution, molecular biology and clinical significance as a human pathogen

Canine Angiostrongylus vasorum-Induced Early Innate Immune Reactions Based on NETs Formation and Canine Vascular Endothelial Cell Activation In Vitro

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