Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
BACKGROUND & AIMS: Nutrients influence non-alcoholic fatty liver disease. Essential fatty acids deficiency promotes various syndromes, including hepatic steatosis, through increased de novo lipogenesis. The mechanisms underlying such increased lipogenic response remain unidentified. METHODS: We used wild type mice and mice lacking Liver X Receptors to perform a nutrigenomic study that aimed at examining the role of these transcription factors. RESULTS: We showed that, in the absence of Liver X Receptors, essential fatty acids deficiency does not promote steatosis. Consistent with this, Liver X Receptors are required for the elevated expression of genes involved in lipogenesis in response to essential fatty acids deficiency. CONCLUSIONS: This work identifies, for the first time, the central role of Liver X Receptors in steatosis induced by essential fatty acids deficiency.
ISSN: 0168-8278

inserm-00872314
http://www.hal.inserm.fr/inserm-00872314
DOI : 10.1016/j.jhep.2013.01.006
PUBMED : 23333450

Éditeur(s) : HAL CCSD
Résumé : Staphylococcus aureus can cause a wide range of infections in humans and warm-blooded animals. The epithelial surface is the principal site of staphylococcal infection. The goal of this work was to investigate the cytopathic effect of S. aureus and its ability to affect host cell cycle. Cultures of human cervix cancer HeLa and mammary gland bovine MAC-T epithelial cells were used to study in vitro the effects of S. aureus strains from human or ruminant origins. Using microscopic examination, we found that S. aureus induced an enlargement of the host cells and we observed that S. aureus slowed down cell proliferation. Similar effect was observed on both human and bovine cells using the human or the ruminant strains. Microscopic analysis of DAPI-stained cells revealed huge decrease of mitotic indexes in infected HeLa and Mac-T cells, synchronized by Double Thymidine Block. Flow cytometry analysis showed that S. aureus induces G2/M phase delay in synchronous HeLa cells. Western blot analysis revealed that the G2/M phase delay was associated with an accumulation of inactive phosphorylated cyclin-dependent kinase Cdk1/cdc2, a key inducer of mitosis entry, and dephosphorylation of core histone H3, an important component of the epigenetic landscape. Altogether, these results suggest that the delay in G2/M phase transition of the infected epithelial cells may be one of the mechanisms employed by S. aureus to survive and to propagate inside the host. Further investigations are ongoing to fully understand the mechanisms associated to this type of S. aureus-host cell interactions.
International Symposium on Staphylococci and Staphylococcal Infections -ISSSI-2012
Lyon, France

hal-01209356
https://hal.archives-ouvertes.fr/hal-01209356
PRODINRA : 173265

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Staphylococcus aureus is a highly versatile, opportunistic pathogen and the etiological agent of a wide range of infections in humans and warm-blooded animals. The epithelial surface is its principal site of colonization and infection. In this work, we investigated the cytopathic effect of S. aureus strains from human and animal origins and their ability to affect the host cell cycle in human HeLa and bovine MAC-T epithelial cell lines. S. aureus invasion slowed down cell proliferation and induced a cytopathic effect, resulting in the enlargement of host cells. A dramatic decrease in the number of mitotic cells was observed in the infected cultures. Flow cytometry analysis revealed an S. aureus-induced delay in the G2/M phase transition in synchronous HeLa cells. This delay required the presence of live S. aureus since the addition of the heat-killed bacteria did not alter the cell cycle. The results of Western blot experiments showed that the G2/M transition delay was associated with the accumulation of inactive cyclin-dependent kinase Cdk1, a key inducer of mitosis entry, and with the accumulation of unphosphorylated histone H3, which was correlated with a reduction of the mitotic cell number. Analysis of S. aureus proliferation in asynchronous, G1- and G2-phase-enriched HeLa cells showed that the G2 phase was preferential for bacterial infective efficiency, suggesting that the G2 phase delay may be used by S. aureus for propagation within the host. Taken together, our results divulge the potential of S. aureus in the subversion of key cellular processes such as cell cycle progression, and shed light on the biological significance of S. aureus-induced host cell cycle alteration.
ISSN: 1932-6203

hal-00873672
https://hal.archives-ouvertes.fr/hal-00873672
https://hal.archives-ouvertes.fr/hal-00873672/document
https://hal.archives-ouvertes.fr/hal-00873672/file/Staphylococcus_aureus-Induced.accepted.pdf
DOI : 10.1371/journal.pone.0063279

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
: In South America, disseminated histoplasmosis due to Histoplasma capsulatum var. capsulatum (H. capsulatum), is a severe and frequent opportunistic infection in AIDS patients. In areas outside the USA where specific-Histoplasma antigen detection is not available, the diagnosis is difficult. With the galactomannan antigen (GM) detection, a test commonly used for invasive aspergillosis diagnosis, there is a cross-reactivity with H. capsulatum that can be helpful for the diagnosis of histoplasmosis. The aim of this study was to evaluate the GM detection for the diagnosis of disseminated histoplasmosis in AIDS patients. The performance of the GM detection was evaluated with serum collected in French Guiana where H. capsulatum is highly endemic. Sera from AIDS patients with disseminated histoplasmosis occurring from 2002 to 2009 and from control HIV-positive patients without histoplasmosis were tested with the GM detection and Histoplasma-specific antibody detection (IEP). In 39 AIDS patients with proven disseminated histoplasmosis, the sensitivity of the Histoplasma IEP was only 35.9% and was linked to the TCD4+ lymphocyte level. For the GM detection, the sensitivity (Se) was 76.9% and specificity (Sp) was 100% with the recommended threshold for aspergillosis diagnosis (0.5). The test was more efficient with a threshold of 0.4 (Se: 0.82 [95% CI: 0.66-0.92], Sp: 1.00 [95% CI: 0.86-1.00], LR+: >10, LR-: 0.18). This study confirms that the GM detection can be a surrogate marker for the diagnosis of disseminated histoplasmosis in AIDS patients in endemic areas where Histoplasma EIA is not available.
ISSN: 1438-4221

inserm-01065096
http://www.hal.inserm.fr/inserm-01065096
http://www.hal.inserm.fr/inserm-01065096/document
http://www.hal.inserm.fr/inserm-01065096/file/2014_Iriart_-_Complementary_tool_for_managementsur histo_infections_in_AID.pdf
DOI : 10.1016/j.ijmm.2014.07.016

Éditeur(s) : HAL CCSD
Résumé : absent
16. International Symposium on Staphylococci and Staphylococcal Infections
Chicago, United States

hal-01209709
https://hal.archives-ouvertes.fr/hal-01209709
PRODINRA : 269852