Iron overload exacerbates experimental meningoencephalitis by Cryptococcus neoformans

Barluzzi, Roberta; Saleppico, Silvia; Nocentini, Angela; Boelaert, Johan R.; Neglia, Rachele Giovanna; Bistoni, Francesco; Blasi, Elisabetta

doi:10.1016/s0165-5728(02)00324-7

Cited by 37 publications

(32 citation statements)

References 35 publications

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“…Likewise, mice supplemented with iron and intracerebrally infected with C. neoformans showed increased fungal burden and reduced IL-12 production throughout the infection and low levels of IFN-g especially in the late stages of the infection relative to untreated control animals. 76 In healthy individuals, the brain is devoid of antibodies given that the BBB is intact and prevents these relatively large molecules from entering the CNS. 77, 78 Yet, in cerebral inflammation, the BBB is disrupted and becomes increasingly permeable to these opsonins which pass through to help fight infections, augmenting the microglial anti-cryptococcal activity.…”

Section: Opportunistic Fungal Infectionsmentioning

confidence: 99%

Role of microglia in fungal infections of the central nervous system

2016

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Most fungi are capable of disseminating into the central nervous system (CNS) commonly being observed in immunocompromised hosts. Microglia play a critical role in responding to these infections regulating inflammatory processes proficient at controlling CNS colonization by these eukaryotic microorganisms. Nonetheless, it is this inflammatory state that paradoxically yields cerebral mycotic meningoencephalitis and abscess formation. As peripheral macrophages and fungi have been investigated aiding our understanding of peripheral disease, ascertaining the key interactions between fungi and microglia may uncover greater abilities to treat invasive fungal infections of the brain. Here, we present the current knowledge of microglial physiology. Due to the existing literature, we have described to greater extent the opportunistic mycotic interactions with these surveillance cells of the CNS, highlighting the need for greater efforts to study other cerebral fungal infections such as those caused by geographically restricted dimorphic and rare fungi.

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Section: Opportunistic Fungal Infectionsmentioning

confidence: 99%

Role of microglia in fungal infections of the central nervous system

2016

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“…24, 25 The iron metabolism has been described in C. neoformans , 26–32 showing important roles in the proliferation of C. neoformans and establishment of cryptococcosis. 28, 33 For C. gattii , however, limited information are available regarding its iron metabolism. 34 …”

Section: Introductionmentioning

confidence: 99%

Proteomic Profiling of the Influence of Iron Availability on Cryptococcus gattii

et al. 2011

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Iron is essential and ubiquitous in living organisms. The competition for this micronutrient between the host and its pathogens has been related to disease establishment. Cryptococcus gattii is an encapsulated yeast that causes cryptococcosis mainly in immunocompetent individuals. In this study, we analyzed the proteomic profile of the C. gattii R265 Vancouver Island isolate under iron-depleted and –replete conditions by Multidimensional Protein Identification Technology (MudPIT) and by 2D-GE. Proteins and key mechanisms affected by alteration of iron levels such as capsule production, cAMP-signaling pathway, response to stress, and metabolic pathways related to mitochondrial function were identified. Our results also show both proteomic methodologies employed to be complementary.

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“…Iron availability influences at least two major virulence traits in this fungus, including the production of a polysaccharide capsule and deposition of melanin in the cell wall (2,3,4,5,6). Additionally, iron overload exacerbates cryptococcal disease in a mouse model of cryptococcosis (7). Like other pathogens, C. neoformans must compete with mammalian iron sequestration mechanisms and proteins to obtain iron during infection.…”

mentioning

confidence: 99%

Cryptococcus neoformans Requires the ESCRT Protein Vps23 for Iron Acquisition from Heme, for Capsule Formation, and for Virulence

et al. 2013

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Iron availability is a key regulator of virulence factor elaboration in Cryptococcus neoformans, the causative agent of fungal meningoencephalitis in HIV/AIDS patients. In addition, iron is an essential nutrient for pathogen proliferation in mammalian hosts but little is known about the mechanisms of iron sensing and uptake in fungal pathogens that attack humans. In this study, we mutagenized C. neoformans by Agrobacterium-mediated T-DNA insertion and screened for mutants with reduced growth on heme as the sole iron source. Among 34 mutants, we identified a subset with insertions in the gene for the ESCRT-I (endosomal sorting complex required for transport) protein Vps23 that resulted in a growth defect on heme, presumably due to a defect in uptake via endocytosis or misregulation of iron acquisition from heme. Remarkably, vps23 mutants were also defective in the elaboration of the cell-associated capsular polysaccharide that is a major virulence factor, while overexpression of Vps23 resulted in cells with a slightly enlarged capsule. These phenotypes were mirrored by a virulence defect in the vps23 mutant in a mouse model of cryptococcosis and by hypervirulence of the overexpression strain. Overall, these results reveal an important role for trafficking via ESCRT functions in both heme uptake and capsule formation, and they further reinforce the connection between iron and virulence factor deployment in C. neoformans.

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Iron overload exacerbates experimental meningoencephalitis by Cryptococcus neoformans

Cited by 37 publications

References 35 publications

Role of microglia in fungal infections of the central nervous system

Role of microglia in fungal infections of the central nervous system

Proteomic Profiling of the Influence of Iron Availability on Cryptococcus gattii

Cryptococcus neoformans Requires the ESCRT Protein Vps23 for Iron Acquisition from Heme, for Capsule Formation, and for Virulence

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