Biomedical subjects

Caroline Clair

Publications and source records attributed to Caroline Clair.

3 recordsLinked to original sources

PubMed2004

Calcium signalling during cell interactions with bacterial pathogens.

The ability of a pathogenic microorganism to cause a disease is conditioned by its ability to colonise a given niche and implicates the expression of specific determinants, i.e. virulence factors, that allow the pathogen to adhere to or to invade epithelial cells. Diseases may be induced by bacteria that replicate extracellularly and alter the epithelial mucosa by producing toxins. Ca2+ signalling has been implicated in various steps of bacterial infection. Bacterial toxins can induce an increase in free cytosolic Ca2+ in host cells, itself required for the toxin-mediated effects. Such toxins, by diffusing in the extracellular media, can act at a distance from the site of infection and have a global effect on the integrity of the epithelium by promoting the expression of pro-inflammatory cytokines. Independent on toxins, bacteria can induce Ca2+ responses that play a role in cytoskeletal rearrangements required for cell binding or internalisation of the microorganism. In some instances, invasion of the epithelium may be followed by bacterial access to deeper tissue, dissemination to other organs, and sometimes persistence in host cells in a parasitic-like mode. Such strategies underline the pathogen abilities to control innate defence cells such as professional phagocytes, and may implicate the diversion of Ca(2+)-dependent cellular processes that normally result in killing of the ingested bacteria. Finally, bacterial pathogens can also induce the cell release of ATP, a Ca2+ agonist, that may expand bacterial cell signalling by a paracrine or autocrine route, leading to enhanced colonisation or enhanced host cell responses to the invading microorganism.

Animals↗

PubMed2003

Hormone receptor gradients supporting directional Ca2+ signals: direct evidence in rat hepatocytes.

BACKGROUND/AIMS: In the liver, InsP(3)-dependent agonists such as vasopressin and noradrenaline induce tightly coordinated sequences of intracellular Ca(2+) increases, leading to apparent unidirectional Ca(2+) waves. In previous works, we have postulated that cell-to-cell differences in hormone receptor density create a cellular sensitivity gradient that determines which cell initiates the intercellular Ca(2+) wave and the direction of propagation of the Ca(2+) signal. The aim of this study was to test directly this hypothesis. METHODS: Lobular distribution of V1a vasopressin receptors and alpha1 adrenergic receptors were observed by autoradiography in rat liver sections. Cell-to-cell differences in the number of these receptors were evaluated on hepatocyte multiplets using specific fluorescent probes. RESULTS: The relative amount of fluorescence associated with the V1a receptor differed significantly between cells within multiplets. The 'cell-after-cell' Ca(2+) increase induced by vasopressin was correlated with the number of V1a receptors. These observations may be more general, as autoradiography revealed similar lobular distributions of V1a receptors and alpha1 adrenergic receptors; the amounts of both were greatest in hepatocytes surrounding central veins. CONCLUSIONS: These data confirm that a fine gradient along liver cell plates contributes to the molecular basis of the unidirectional hormone-induced Ca(2+) signalling observed in the liver lobule.

Animals↗

PubMed2003

Connexin-dependent inter-cellular communication increases invasion and dissemination of Shigella in epithelial cells.

Shigella flexneri, the causative agent of bacillar dystentery, invades the colonic mucosa where it elicits an intense inflammatory reaction responsible for destruction of the epithelium. During cell invasion, contact with host cells activates the type-III secretion of the Shigella IpaB and IpaC proteins. IpaB and IpaC are inserted into host cell plasma membranes and trigger initial signals that result in actin polymerization, while allowing cytosolic access of other bacterial effectors that further reorganize the cytoskeleton. After internalization, Shigella moves intracellularly and forms protrusions that infect neighbouring cells, promoting bacterial dissemination across the epithelium. Here, we show that during cell invasion, Shigella induces transient peaks in intracellular calcium concentration that are dependent on a functional type-III secretory apparatus. In addition, Shigella invasion induces the opening of Connexin 26 (Cx26) hemichannels in an actin- and phospholipase-C-dependent manner, allowing release of ATP into the medium. The released ATP, in turn, increases bacterial invasion and spreading, as well as calcium signalling induced by Shigella. These results provide evidence that pathogen-induced opening of connexin channels promotes signalling events that favour bacterial invasion and dissemination.

Actins↗