Biology subjects

Mignon, V.

Publications and source records attributed to Mignon, V..

2 recordsLinked to original sources

bioRxiv2022

Specific interaction between Group B Streptococcus CC17 hypervirulent clone and phagocytes

Streptococcus agalactiae also named Group B Streptococcus (GBS) is the most significant pathogen causing invasive infections, such as bacteremia and meningitis, in neonates. Worldwide epidemiological studies have shown that a particular clonal complex (CC) of capsular serotype III, the CC17, is strongly associated with meningitis in neonates and is therefore designated as the hypervirulent clone. Macrophages are a permissive niche for intracellular bacteria of all GBS clones. In this study we deciphered the specific interaction of GBS CC17 strains with macrophages. Our study revealed that CC17 strains are phagocytosed at a higher rate than GBS non-CC17 strains by human monocytes and macrophages both in cellular models and primary cells. CC17 enhanced phagocytosis is due to an initial enhanced-attachment step to macrophages mediated by the CC17 specific surface protein HvgA and the PI-2b pilus (Spb1). We showed that two different inhibitors of scavenger receptors (fucoidan and poly(I)) specifically inhibited CC17 adhesion and phagocytosis while not affecting those of non-CC17 strains. Once phagocytosed, both CC17 and non-CC17 strains remained in a LAMP-1 positive vacuole that ultimately fuses with lysosomes where they can survive at similar rates. Finally, both strains displayed a basal egress which occurs independently from actin and microtubule networks. Our findings provide new insights into the interplay between the hypervirulent GBS CC17 and major players of the hosts innate immune response. This enhanced adhesion leading to higher phagocytosis could reflect a peculiar capacity of the CC17 lineage to subvert the host immune defenses, establish a niche for persistence or disseminate.

microbiology↗

bioRxiv2021

Megalencephalic leukoencephalopathy with subcortical cysts is a developmental disorder of the gliovascular unit

Absence of the astrocyte-specific membrane protein MLC1 is responsible for megalencephalic leukoencephalopathy with subcortical cysts (MLC); this rare type of leukodystrophy is characterized by early-onset macrocephaly and progressive white matter vacuolation that lead to ataxia, spasticity, and cognitive decline. During postnatal development (from P5 to P15 in the mouse), MLC1 forms a membrane complex with GlialCAM (another astrocytic transmembrane protein) at the junctions between perivascular astrocytic processes (PvAPs, which along with blood vessels form the gliovascular unit (GVU)). We analyzed the GVU in the Mlc1 knock-out mouse model of MLC. The absence of MLC1 led to an accumulation of fluid in the brain but did not modify the endothelial organization or the integrity of the blood-brain barrier. From P10 onward, the postnatal acquisition of vascular smooth muscle cell contractility was altered, resulting in a marked reduction in arterial perfusion and neurovascular coupling. These anomalies were correlated with alterations in astrocyte morphology, astrocyte polarity and the structural organization of the PvAPs perivascular coverage, and poor intraparenchymal circulation of the cerebrospinal fluid (CSF). Hence, MLC1 is required for the postnatal development and organization of PvAPs and controls vessel contractility and intraparenchymal interstitial fluid clearance. Our data suggest that (i) MLC is a developmental disorder of the GVU, and (ii) PvAP and VSMC maturation defects are primary events in the pathogenesis of MLC and therapeutic targets for this disease.

neuroscience↗