Ab binding alters gene expression in Cryptococcus neoformans and directly modulates fungal metabolism

McClelland, Erin E.; Nicola, André Moraes; Prados-Rosales, Rafael; Casadevall, Arturo

doi:10.1172/jci38322

Cited by 96 publications

(98 citation statements)

References 38 publications

(39 reference statements)

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“…These C. neoformans protective glucuronoxylomannan-specific IgG MAbs seem to work in cooperation with nitric oxide, and both Th1 and Th2 cytokines [64,65]. In addition, binding of protective glucuronoxylomannan-reactive 18B78 IgG MAb and IgM MAbs (12A1 and 13F1) to C. neoformans also modifies the gene expression of the fungi, phosphorylation of proteins and lipid metabolism [66]. (Fig.…”

Section: Demonstration Of Protective Role Of Antibodies In Fungal Infmentioning

confidence: 97%

The protective role of immunoglobulins in fungal infections and inflammation

2014

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International audienceIncreased incidence of fungal infections in the immunocompromised individuals and fungi-mediated allergy and inflammatory conditions in immunocompetent individuals is a cause of concern. Consequently, there is a need for efficient therapeutic alternatives to treat fungal infections and inflammation. Several studies have demonstrated that antibodies or immunoglobulins have a role in restricting the fungal burden and their clearance. However, based on the data from monoclonal antibodies, it is now evident that the efficacy of antibodies in fungal infections is dependent on epitope specificity, abundance of protective antibodies, and their isotype. Antibodies confer protection against fungal infections by multiple mechanisms that include direct neutralization of fungi and their antigens, inhibition of growth of fungi, modification of gene expression, signaling and lipid metabolism, causing iron starvation, inhibition of polysaccharide release, and biofilm formation. Antibodies promote opsonization of fungi and their phagocytosis, complement activation, and antibody-dependent cell toxicity. Passive administration of specific protective monoclonal antibodies could also prove to be beneficial in drug resistance cases, to reduce the dosage and associated toxic symptoms of anti-fungal drugs. The longer half-life of the antibodies and flexibilities to modify their structure/forms are additional advantages. The clinical data obtained with two monoclonal antibodies should incite interests in translating pre-clinical success into the clinics. The anti-inflammatory and immunoregulatory role of antibodies in fungal inflammation could be exploited by intravenous immunoglobulin or IVIg

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Section: Demonstration Of Protective Role Of Antibodies In Fungal Infmentioning

confidence: 97%

The protective role of immunoglobulins in fungal infections and inflammation

2014

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“…However, in their study in this issue of the JCI, McClelland et al advance an intriguing conceptual paradigm that binding of specific antibodies alone can elicit a range of metabolic perturbations in the fungal pathogen Cryptococcus neoformans (2). C. neoformans, widespread in the environment, is well-controlled and rarely symptomatic in healthy individuals, in large part because of antibody-dependent mechanisms.…”

Section: Evolving Concepts Of Antibody Defensementioning

confidence: 99%

“…However, the organism causes recalcitrant disease and high mortality in patients with advanced cell-mediated immunodeficiency, such as those individuals with HIV/AIDS who have very low CD4 + T cell counts and patients who have undergone solid organ transplantation (3,4). McClelland and colleagues show that three antibodies that bind to distinct topological sites on the polysaccharide capsule of C. neoformans elicit varying effects on its gene expression (2). The effects are direct and due to the antibodies in the absence of other soluble or cellular host elements, providing evidence that pathogens can recognize and respond to antibody binding by modulating distinct microbial genetic pathways ( Figure 1B).…”

Section: Evolving Concepts Of Antibody Defensementioning

confidence: 99%

“…McClelland and colleagues undertook an in vitro systems biology analysis of the biochemical and biological effects mediated by mAb binding to the polysaccharide capsule of C. neoformans (2). An important first experiment assessed whether binding of the capsule-specific mAbs to C. neoformans cells induced alterations in gene expression, as assessed by microarray analysis of mRNA.…”

Section: Genetic Bridge To the Futurementioning

confidence: 99%

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Pathogen-specific antibodies: codependent no longer

Janoff

Frank²

2010

J. Clin. Invest.

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“…These reports yielded important insights into the kinetics of capsule synthesis, but all suffered from an important caveat: because antibodies and complement proteins interact directly with capsule components, they may change its physical properties, especially at the reasonably high concentrations needed for the observations. Indeed, antibody binding increases rigidity of the capsule to a point that can actually hinder budding of daughter cells [7] and it induces metabolic alterations in the fungal cell [8]. Hence, it is possible that these antibody effects affected the kinetics of capsule growth and there is a need for additional approaches to study capsule dynamics.…”

mentioning

confidence: 99%