Biology subjects

Mantovani, A.

Publications and source records attributed to Mantovani, A..

3 recordsLinked to original sources

bioRxiv2022

Regulation of inflammation and protection against invasive pneumococcal infection by the long pentraxin PTX3

Streptococcus pneumoniae is a major pathogen in children, elderly subjects and immunodeficient patients. PTX3 is a fluid phase pattern recognition molecule (PRM) involved in resistance to selected microbial agents and in regulation of inflammation. The present study was designed to assess the role of PTX3 in invasive pneumococcal infection. In a murine model of invasive pneumococcal infection, PTX3 was strongly induced in non-hematopoietic (particularly, endothelial) cells. The IL-1{beta}/MyD88 axis played a major role in regulation of the Ptx3 gene expression. Ptx3-/- mice were more susceptible to invasive pneumococcal infection. Although high concentrations of PTX3 had opsonic activity in vitro, no evidence of PTX3-enhanced phagocytosis was obtained in vivo. In contrast, Ptx3-deficient mice showed enhanced recruitment of neutrophils and inflammation. Using P-selectin deficient mice, we found that protection against pneumococcus was dependent upon PTX3-mediated regulation of neutrophil inflammation. In humans, PTX3 genetic polymorphisms were associated with invasive pneumococcal infections. Thus, this fluid phase PRM plays an important role in tuning inflammation and resistance against invasive pneumococcal infection.

immunology↗

bioRxiv2022

Classification of Movement-Related Oscillations in sEEG Recordings with Machine Learning

Previous electrophysiological research has characterized canonical oscillatory patterns associated with movement mostly from recordings of primary sensorimotor cortex. Less work has attempted to decode movement based on electrophysiological recordings from a broader array of brain areas such as those sampled by stereoelectroencephalography (sEEG). Here we decoded movement using a linear support vector machine (SVM). We were able to accurately classify sEEG spectrograms during a keypress movement in a task versus those during the inter-trial interval. Furthermore, the important time-frequency patterns for this classification recapitulated findings from previous studies that used non-invasive electroencephalography (EEG) and electrocorticography (ECoG) and identified brain regions that were not associated with movement in previous studies. Specifically, we found these previously described patterns: beta (13 - 30 Hz) desynchronization, beta synchronization (rebound), pre-movement alpha (8 - 15 Hz) modulation, a post-movement broadband gamma (60 - 90 Hz) increase and an event-related potential. These oscillatory patterns were newly observed in a wide range of brain areas accessible with sEEG that are not accessible with other electrophysiology recording methods. For example, the presence of beta desynchronization in the frontal lobe was more widespread than previously described, extending outside primary and secondary motor cortices. We provide evidence for a system of putative motor networks that exhibit unique oscillatory patterns by describing the anatomical extent of the movement-related oscillations that were observed most frequently across all sEEG contacts. Significance StatementSeveral major motor networks have been previously delineated in humans, however, much less is known about the population-level oscillations that coordinate this neural circuitry, especially in cortex. Therapies that modulate brain circuits to treat movement disorders, such as deep brain stimulation (DBS), or use brain signals to control movement, such as brain-computer interfaces (BCIs), rely on our basic scientific understanding of this movement neural circuitry. In order to bridge this gap, we used stereoelectroencephalography (sEEG) collected in human patients being monitored for epilepsy to assess oscillatory patterns during movement.

neuroscience↗

bioRxiv2021

SARS-CoV-2-associated ssRNAs activate inflammation and immunity via TLR7/8

The inflammatory and IFN pathways of innate immunity play a key role in both resistance and pathogenesis of Coronavirus Disease 2019 (COVID-19). Innate sensors and SARS-CoV-2-Associated Molecular Patterns (SAMPs) remain to be completely defined. Here we identify single-stranded RNA (ssRNA) fragments from SARS-CoV-2 genome as direct activators of endosomal TLR7/8 and MyD88 pathway. The same sequences induced human DC activation in terms of phenotype and functions, such as IFN and cytokine production and Th1 polarization. A bioinformatic scan of the viral genome identified several hundreds of fragments potentially activating TLR7/8, suggesting that products of virus endosomal processing potently activate the IFN and inflammatory responses downstream these receptors. In vivo, SAMPs induced MyD88-dependent lung inflammation characterized by accumulation of proinflammatory and cytotoxic mediators and immune cell infiltration, as well as splenic DC phenotypical maturation. These results identify TLR7/8 as crucial cellular sensors of ssRNAs encoded by SARS-CoV-2 involved in host resistance and disease pathogenesis of COVID-19.

immunology↗