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An Alpha-Glucan from Lomentospora prolificans Mediates Fungal-Host Interaction Signaling through Dectin-1 and Mincle.

ABSTRACT: Scedosporium and Lomentospora are a group of filamentous fungi with some clinically relevant species causing either localized, invasive, or disseminated infections. Understanding how the host immune response is activated and how fungi interact with the host is crucial for a better management of the infection. In this context, an α-glucan has already been described in S. boydii, which plays a role in the inflammatory response. In the present study, an α-glucan has been characterized in L. prolificans and was shown to be exposed on the fungal surface. The α-glucan is recognized by peritoneal macrophages and induces oxidative burst in activated phagocytes. Its recognition by macrophages is mediated by receptors that include Dectin-1 and Mincle, but not TLR2 and TLR4. These results contribute to the understanding of how Scedosporium's and Lomentospora's physiopathologies are developed in patients suffering with scedosporiosis and lomentosporiosis.

SUBMITTER: Xisto MIDDS

PROVIDER: S-EPMC10054066 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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An Alpha-Glucan from Lomentospora prolificans Mediates Fungal-Host Interaction Signaling through Dectin-1 and Mincle.

Xisto Mariana Ingrid Dutra da Silva MIDDS Dias Lucas Dos Santos LDS Bezerra Francisco Felipe FF Bittencourt Vera Carolina Bordallo VCB Rollin-Pinheiro Rodrigo R Cartágenes-Pinto Ana Carolina AC Haido Rosa Maria Tavares RMT Mourão Paulo Antônio de Souza PAS Barreto-Bergter Eliana E

Journal of fungi (Basel, Switzerland) 20230223 3

Scedosporium and Lomentospora are a group of filamentous fungi with some clinically relevant species causing either localized, invasive, or disseminated infections. Understanding how the host immune response is activated and how fungi interact with the host is crucial for a better management of the infection. In this context, an α-glucan has already been described in S. boydii, which plays a role in the inflammatory response. In the present study, an α-glucan has been charac ...[more]

PMID: 36983458

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Project description:Abstract Background Management of Scedosporium/Lomentospora prolificans infections remains challenging. We described predisposing factors, clinical manifestations, and outcomes of these rare mold infections, including predictors of early (1-month) and late (18-month) all-cause mortality and treatment failure. Methods We conducted a retrospective Australian-based observational study of proven/probable Scedosporium/L prolificans infections from 2005 to 2021. Data on patient comorbidities, predisposing factors, clinical manifestations, treatment, and outcomes up to 18 months were collected. Treatment responses and death causality were adjudicated. Subgroup analyses, multivariable Cox regression, and logistic regression were performed. Results Of 61 infection episodes, 37 (60.7%) were attributable to L prolificans. Forty-five of 61 (73.8%) were proven invasive fungal diseases (IFDs), and 29 of 61 (47.5%) were disseminated. Prolonged neutropenia and receipt of immunosuppressant agents were documented in 27 of 61 (44.3%) and 49 of 61 (80.3%) episodes, respectively. Voriconazole/terbinafine was administered in 30 of 31 (96.8%) L prolificans infections, and voriconazole alone was prescribed for 15 of 24 (62.5%) Scedosporium spp infections. Adjunctive surgery was performed in 27 of 61 (44.3%) episodes. Median time to death post–IFD diagnosis was 9.0 days, and only 22 of 61 (36.1%) attained treatment success at 18 months. Those who survived beyond 28 days of antifungal therapy were less immunosuppressed with fewer disseminated infections (both P < .001). Disseminated infection and hematopoietic stem cell transplant were associated with increased early and late mortality rates. Adjunctive surgery was associated with lower early and late mortality rates by 84.0% and 72.0%, respectively, and decreased odds of 1-month treatment failure by 87.0%. Conclusions Outcomes associated with Scedosporium/L prolificans infections is poor, particularly with L prolificans infections or in the highly immunosuppressed population. Higher rates of mortality and treatment failure were observed in Lomentospora prolificans infections or in the highly immunosuppressed patients with hematological malignancy or hematopoietic stem cell transplant. Adjunctive surgery was associated with lower mortality and decreased odds of 1-month treatment failure.

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An Alpha-Glucan from Lomentospora prolificans Mediates Fungal-Host Interaction Signaling through Dectin-1 and Mincle.

Publications

An Alpha-Glucan from <i>Lomentospora prolificans</i> Mediates Fungal-Host Interaction Signaling through Dectin-1 and Mincle.

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