Zygomycotic invasion of the central nervous system

Sasaki, Tomoaki; Mineta, Masayuki; Kobayashi, Keigo; Ando, Motomi; Obata, Masahiko

doi:10.1007/s11604-010-0435-z

Cited by 9 publications

(8 citation statements)

References 10 publications

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“…Furthermore, haemorrhage has been observed following an aneurysm caused by Mucor infection in an immuno-compromised patient with primary mucormycosis (36). Similarly, mycotic aneurysm, vasculitis and also blood vessel occlusion were observed in zygomycosis infection (37), suggesting a trapping of fungal cells and blood vessel damage may occur in different fungal species infection.…”

Section: Discussionmentioning

confidence: 95%

Blood vessel occlusion byCryptococcus neoformansis a mechanism for haemorrhagic dissemination of infection

Jf¹,

Bojarczuk²,

Rl³

et al. 2020

Preprint

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24Meningitis caused by infectious pathogens are associated with vessel damage and infarct 25 formation, however the physiological cause is unknown. Cryptococcus neoformans, is a 26 human fungal pathogen and causative agent of cryptococcal meningitis, where vascular 27 events are observed in up to 30% of cases, predominantly in severe infection. Therefore, we 28 aimed to investigate how infection may lead to vessel damage and associated pathogen 29 dissemination using a zebrafish model for in vivo live imaging. We find that cryptococcal 30 cells become trapped within the vasculature (dependent on there size) and proliferate there 31 resulting in vasodilation. Localised cryptococcal growth, originating from a single or small 32 number of cryptococcal cells in the vasculature was associated with sites of dissemination 33 and simultaneously with loss of blood vessel integrity. Using a cell-cell junction tension 34 reporter we identified dissemination from intact blood vessels and where vessel rupture 35 occurred. Finally, we manipulated blood vessel stifness via cell junctions and found 36 increased stiffness resulted in increased dissemination. Therefore, global vascular 37 vasodilation occurs following infection, resulting in increased vessel tension which 38 subsequently increases dissemination events, representing a positive feedback loop. Thus, 39 we identify a mechanism for blood vessel damage during cryptococcal infection that may 40 represent a cause of vascular damage and cortical infarction more generally in infective 41 meningitis. 42 43 44 45 46 47 48 Introduction 49 Life threatening systemic infection commonly results from tissue invasion requiring 50 dissemination of microbes, usually via the blood stream. Blood vessel damage and blockage 51 are commonly associated with blood infection, as exemplified by mycotic (infective) 52 aneurisms or sub-arachnoid haemorrhage (1). Indeed, both bacterial and fungal meningitis 53 are associated with vascular events including vasculitis, aneurisms and infarcts (1-5). 54The mechanisms of dissemination to the brain in meningitis have been extensively studied in 55 vitro and in vivo. Experimental studies suggest three potential mechanisms: passage of the 56 pathogen between cells of the blood brain barrier, polarised endocytosis and exocytosis of 57 the pathogen by brain vascular endothelial cells, and passage through the blood brain 58 barrier inside immune cells. However, we hypothesised that blood vessel blockage and 59 haemorrhagic dissemination might be an alternative mechanism. 60Cryptococcus neoformans is an opportunistic fungal pathogen causing life threatening 61 cryptococcal meningitis in severely immunocompromised patients. C. neoformans is a 62 significant pathogen of HIV/AIDs positive individuals with cryptococcal meningitis ultimately 63 responsible for 15% of all AIDS related deaths worldwide (6). C . neoformans has 64 previsously been suggested to disseminate from the blood stream into the brain through 65 different routes, including transcytosis, and by...

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Section: Discussionmentioning

confidence: 95%

Blood vessel occlusion byCryptococcus neoformansis a mechanism for haemorrhagic dissemination of infection

Jf¹,

Bojarczuk²,

Rl³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Furthermore, haemorrhage has been observed following an aneurysm caused by Mucor infection in an immuno-compromised patient with primary mucormycosis [ 38 ]. Similarly, mycotic aneurysm, vasculitis and also blood vessel occlusion were observed in zygomycosis infection [ 39 ], suggesting a trapping of fungal cells and blood vessel damage may occur in different fungal species infection.…”

Section: Discussionmentioning

confidence: 99%

Blood vessel occlusion by Cryptococcus neoformans is a mechanism for haemorrhagic dissemination of infection

et al. 2022

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Meningitis caused by infectious pathogens is associated with vessel damage and infarct formation, however the physiological cause is often unknown. Cryptococcus neoformans is a human fungal pathogen and causative agent of cryptococcal meningitis, where vascular events are observed in up to 30% of patients, predominantly in severe infection. Therefore, we aimed to investigate how infection may lead to vessel damage and associated pathogen dissemination using a zebrafish model that permitted noninvasive in vivo imaging. We find that cryptococcal cells become trapped within the vasculature (dependent on their size) and proliferate there resulting in vasodilation. Localised cryptococcal growth, originating from a small number of cryptococcal cells in the vasculature was associated with sites of dissemination and simultaneously with loss of blood vessel integrity. Using a cell-cell junction tension reporter we identified dissemination from intact blood vessels and where vessel rupture occurred. Finally, we manipulated blood vessel tension via cell junctions and found increased tension resulted in increased dissemination. Our data suggest that global vascular vasodilation occurs following infection, resulting in increased vessel tension which subsequently increases dissemination events, representing a positive feedback loop. Thus, we identify a mechanism for blood vessel damage during cryptococcal infection that may represent a cause of vascular damage and cortical infarction during cryptococcal meningitis.

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“…Infection-derived vasculitis is caused by angiogenic pathogens, including Aspergillus sp., Candida albicans, zygomycotina sp., Cryptococcus neoformans, and so on, and their etiopathogenesis can be summarized as follows: subarachnoidal meningitis, sinuses or orbital infection, and immune mechanism in the context of chronic infections (Lampros et al 2021;Herlin et al 2015;Thirunavukkarasu et al 2021). Early recognition and diagnosis of cerebral vasculitis can, to a great extent, alleviate the risk of its severity and improve prognosis (Rao et al 1978a;Jung et al 2018;Salvarani et al 2007;Sasaki et al 2010;Ellis et al 2018).…”

Section: Discussionmentioning

confidence: 99%

“… Died (Laurencikas et al 2006 ) 12 Male Aspergillum antigen test Aspergillus sp. 31 Died (Marazzi et al 2008 ) 5 Male Histological examination Candida albicans 8 Died (Sasaki et al 2010 ) 35 Female Histological examination zygomycotina sp. 115 Died Female Tissue pathology examination - Recovery 68 Female Bacterial culture 28 Died (Martins et al 2010 ) 56 Female Bacterial culture Aspergillus sp.…”

Section: Discussionmentioning

confidence: 99%

Cerebral vasculitis caused by Talaromyces marneffei and Aspergillus niger in a HIV-positive patient: a case report and literature review

Gao

Chen

et al. 2022

J. Neurovirol.

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Cerebral vasculitis is a long-standing but flourishing and fadeless research topic. Infections are a frequent cause of cerebral vasculitis, vital to diagnose due to involvement of specific anti-infection treatments. A 65-year-old man visited the hospital for his neurological symptoms without obvious inducements. After admission, radiological examination and comprehensive conventional microbiological tests (CMTs) revealed suspected intracranial infectious vasculitis. Metagenomic next-generation sequencing (mNGS) and reverse transcription-polymerase chain reaction further confirmed that his cerebral vasculitis was caused by Talaromyces marneffei (T. marneffei) and Aspergillus niger (A. niger) co-infection. The patient’s final diagnosis changed from initial herpetic encephalitis, due to the past history of cephalosome and facial herpes and non-significant antiviral therapeutic effects, to fungal cerebral vasculitis. The patient was discharged after use of targeted antifungal therapies on day 18 of his admission, and his associated symptoms disappeared completely at follow-up 3 weeks later. We first illustrated the presence of uncommon cerebral vasculitis caused by T. marneffei and A. niger in a human immunodeficiency virus-positive patient. In clinically suspected patients with infectious cerebral vasculitis, mNGS should be performed to detect potential pathogens if CMTs may not provide useful pathogenic clues, highlighting the importance of mNGS in the diagnosis and treatment of infectious diseases.

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Zygomycotic invasion of the central nervous system

Cited by 9 publications

References 10 publications

Blood vessel occlusion byCryptococcus neoformansis a mechanism for haemorrhagic dissemination of infection

Blood vessel occlusion byCryptococcus neoformansis a mechanism for haemorrhagic dissemination of infection

Blood vessel occlusion by Cryptococcus neoformans is a mechanism for haemorrhagic dissemination of infection

Cerebral vasculitis caused by Talaromyces marneffei and Aspergillus niger in a HIV-positive patient: a case report and literature review

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