Dataset Information

Efficacy of PTX3 in a rat model of invasive aspergillosis.

ABSTRACT: Pentraxin 3 (PTX3) is an acute-phase glycoprotein with a nonredundant function in the host resistance to Aspergillus fumigatus. PTX3 activity was evaluated against pulmonary aspergillosis in rats immunosuppressed with cortisone acetate. PTX3 enhanced the survival rate and reduced the lung fungal burden of infected rats in both therapeutic and prophylactic modalities. Thus, we extended the protective activity of PTX3 in pulmonary aspergillosis to corticosteroid-induced immunodeficiency, which is a relevant clinical condition in graft-versus-host disease and in solid organ transplant.

SUBMITTER: Lo Giudice P

PROVIDER: S-EPMC2944572 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Efficacy of PTX3 in a rat model of invasive aspergillosis.

Lo Giudice Pietro P Campo Silvia S Verdoliva Antonio A Rivieccio Vincenzo V Borsini Franco F De Santis Rita R Salvatori Giovanni G

Antimicrobial agents and chemotherapy 20100712 10

Pentraxin 3 (PTX3) is an acute-phase glycoprotein with a nonredundant function in the host resistance to Aspergillus fumigatus. PTX3 activity was evaluated against pulmonary aspergillosis in rats immunosuppressed with cortisone acetate. PTX3 enhanced the survival rate and reduced the lung fungal burden of infected rats in both therapeutic and prophylactic modalities. Thus, we extended the protective activity of PTX3 in pulmonary aspergillosis to corticosteroid-induced immunodeficiency, which is ...[more]

PMID: 20625145

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Project description:Background: Aspergillus fumigatus is a ubiquitous saprophytic airborne fungus responsible for more than one million deaths every year. The siderophores of A. fumigatus represent important virulence factors that contribute to the microbiome-metabolome dialog in a host. From a diagnostic point of view, the monitoring of Aspergillus secondary metabolites in urine of a host is promising due to the non-invasiveness, rapidity, sensitivity, and potential for standardization. Methods: Using a model of experimental aspergillosis in immunocompromised Lewis rats, the fungal siderophores ferricrocin (FC) and triacetylfusarinine C (TAFC) were monitored in rat urine before and after lung inoculation with A. fumigatus conidia. Molecular biomarkers in high-dose (HD) and low-dose (LD) infection models were separated using high performance liquid chromatography (HPLC) and were detected by mass spectrometry (MS). In the current work, we corroborated the in vivo MS infection kinetics data with micro-positron emission tomography/computed tomography (?PET/CT) kinetics utilizing 68Ga-labeled TAFC. Results: In the HD model, the initial FC signal reflecting aspergillosis appeared as early as 4 h post-infection. The results from seven biological replicates showed exponentially increasing metabolite profiles over time. In A. fumigatus, TAFC was found to be a less produced biomarker that exhibited a kinetic profile identical to that of FC. The amount of siderophores contributed by the inoculating conidia was negligible and undetectable in the HD and LD models, respectively. In the ?PET/CT scans, the first detectable signal in HD model was recorded 48 h post-infection. Regarding the MS assay, among nine biological replicates in the LD model, three animals did not develop any infection, while one animal experienced an exponential increase of metabolites and died on day 6 post-infection. All remaining animals had constant or random FC levels and exhibited few or no symptoms to the experiment termination. In the LD model, the TAFC concentration was not statistically significant, while the ?PET/CT scan was positive as early as 6 days post-infection. Conclusion: Siderophore detection in rat urine by MS represents an early and non-invasive tool for diagnosing aspergillosis caused by A. fumigatus. ?PET/CT imaging further determines the infection location in vivo and allows the visualization of the infection progression over time.

Dataset Information

Efficacy of PTX3 in a rat model of invasive aspergillosis.

Publications

Efficacy of PTX3 in a rat model of invasive aspergillosis.

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