Biology subjects

Basso, P.

Publications and source records attributed to Basso, P..

4 recordsLinked to original sources

bioRxiv2025

The emerging fungal pathogen Candida auris induces IFNγ to colonize mammalian hair follicles

Public health alarm concerning the emerging fungus Candida auris is fueled by its antifungal drug resistance and propensity to cause deadly outbreaks. Persistent skin colonization drives transmission and lethal sepsis although its basis remains mysterious. We compared the skin colonization dynamics of C. auris with its relative C. albicans, quantifying skin fungal persistence and distribution and immune composition and positioning. C. auris displayed a higher propensity to colonize hair follicles and avidly bound to human hair. While C. albicans triggered an effective sterilizing type 3/17 antifungal immune response driven by IL-17A/F-producing lymphocytes, C. auris triggered a type 1, IFN{gamma}-driven immune response targeting hair follicles. Rather than promoting fungal clearance, IFN{gamma} enhanced C. auris skin colonization by acting directly on keratinocytes impairing epithelial barrier integrity and repressing antifungal defense programs. C. auris exploits focal skin immune responses to create a niche for persistence in hair follicles.

immunology↗

bioRxiv2024

The role of YAP/TAZ signaling in dendritic cell-mediated pathogenesis of insulin resistance and non-alcoholic fatty liver disease

Obesity and insulin resistance (IR) are global health challenges linked to metabolic diseases, such as type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). High-caloric intake, which is associated to NAFLD, induces adipocyte hypertrophy and inflammation, triggering dendritic cell (DC) activation and systemic inflammation. DC exacerbate inflammation by promoting pro-inflammatory responses, aggravating IR and NAFLD progression. NAFLD is characterized by liver fibrosis, which alters tissue stiffness that can trigger mechanosensing pathways such as the Hippo pathway in immune cell types. In this work we explored the roles of key mediators of the Hippo pathway, YAP and TAZ, in DCs within the context of liver fibrosis, obesity and IR, using a model of NAFLD induced by feeding a high fat high sucrose diet. Our findings indicate that specific deletion of YAP and/or TAZ in DCs had minimal impact on IR development and metabolic tissue inflammation. We conclude that YAP and TAZ have limited and possibly redundant roles in the immune pathophysiology of NAFLD and IR.

immunology↗

bioRxiv2022

Deep tissue infection by an invasive human fungal pathogen requires novel lipid-based suppression of the IL-17 response

Candida albicans is the most common cause of human fungal infection, but the mechanisms of invasive pathogenesis remain poorly defined. Here we identify an unexpected mechanism: lipid-mediated immunosuppression. Through forward genetics, we found that C. albicans secretes a lipase, Lip2, that is critical for invasive disease. Murine infection with C. albicans strains that lack Lip2 display an exaggerated host IL-17 response that leads to fungal clearance from solid organs and host survival. IL-17 signaling is required for Lip2 action. The lipase activity of Lip2 inhibits IL-17 production indirectly through suppression of IL-23 production by tissue resident dendritic cells. We conclude that C. albicans suppresses antifungal IL-17 defense in solid organs by altering the tissue lipid milieu.

microbiology↗

bioRxiv2018

Insertion sequences drive the emergence of a highly adapted human pathogen

Taxonomic outliers of Pseudomonas aeruginosa of environmental origin have recently emerged as infectious for humans. Here we present the first genome-wide analysis of an isolate that caused fatal hemorrhagic pneumonia. We demonstrate that, in two sequential clones, CLJ1 and CLJ3, recovered from a patient with chronic pulmonary disease, insertion of a mobile genetic element into the P. aeruginosa chromosome affected major virulence-associated phenotypes and led to increased resistance to antibiotics used to treat the patient. Comparative proteome and transcriptome analyses revealed that this insertion sequence, ISL3, disrupted genes encoding flagellar components, type IV pili, O-specific antigens, translesion polymerase and enzymes producing hydrogen cyanide. CLJ3 possessed seven fold more IS insertions than CLJ1, some modifying its susceptibility to antibiotics by disrupting the genes for the outer-membrane porin OprD and the regulator of {beta}-lactamase expression AmpD. In the Galleria mellonella larvae model, the two strains displayed different levels of virulence, with CLJ1 being highly pathogenic. This work reveals ISs as major players in enhancing the pathogenic potential of a P. aeruginosa taxonomic outlier by modulating both, the virulence and the resistance to antimicrobials, and explains the ability of this bacterium to adapt from the environment to a human host.

microbiology↗