Flux ioniques et energetique cellulaire au cours de l'induction de la competence chez Streptococcus pneumoniae, leur implication dans le transport de l'ADN

CNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc

La mort cellulaire par incompatibilité (caractérisation d'un facteur de transcription bZIP induit lors de la réaction d'incompatibilité chez Podospora anserina)

Chez le champignon filamenteux Podospora anserina, la co-expression de gènes incompatibles (gènes het) dans la même cellule conduit à une réaction de mort cellulaire, l'incompatibilité végétative. Des gènes sont induits lors de l'incompatibilité (gènes idi). Le gène idi-4 code pour un facteur de transcription à motif bZIP, induit en condition d'incompatibilité mais aussi en condition de carence nutritionnelle, en présence de rapamycine, et par différents stress. L'inactivation du gène idi-4 ne supprime pas la réaction de mort cellulaire. Par contre, sa surexpression conduit à une réaction de mort cellulaire apparentée à la réaction de mort celulaire par incompatibilité tant au niveau cytologique qu'au niveau de l'induction des gènes idi. La protéine IDI-4 fixe in vitro une séquence qui ressemble à celle décrite pour d'autres facteurs bZIP. Les promoteurs de certains gènes idi contiennent cette séquence consensus, ils sont donc probablement des cibles directes d'IDI-4.In the filamentous fungus Podospora anserina, co-expression of incompatible genes (het genes) in the same cell leads to a cell death reaction; the vegetative incompatibility. Some genes are induced during incompatibility (idi genes). The idi-4 gene encodes a bZIP transcription factor induced during the incompatibility reaction, but also by nutrient starvation, rapamycin and other stresses. The gene disruption of idi-4 does not suppress the cell death reaction. Conversely, over-expression of idi-4 leads to induction of idi genes and to a cell death reaction similar to cell death by incompatibility at the cytological level. The IDI-4 protein binds in vitro a sequence close to the one described for other bZIP factors. The promoters of some idi genes contain this sequence and so they probably are direct targets of IDI-4.BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Instabilité génétique au locus het-r membre d'une famille de gènes d'incompatibilité

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

autophagie dans la mort cellulaire par incompatibilité et le développement chez Podospora Anserina

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

New onset of myasthenia gravis after treatment of systemic sclerosis by autologous hematopoietic stem cell transplantation : sustained autoimmunity or inadequate reset of tolerance?

Autologous hematopoietic stem-cell transplantation (HSCT) showed promising results for the treatment of primary severe autoimmune diseases (ADs). In this context, development of secondary AD after HSCT has exceptionally been observed, further questioning the roles of patient propensity for AD and of the HSCT procedure. Herein, we report new onset of myasthenia gravis 3 years after successful HSCT in a patient with severe systemic sclerosis, while in complete remission from her first AD. The de novo occurrence of secondary AD (myasthenia gravis) after HSCT was accompanied by the appearance of clonal T-cell expansions measured by the "immunoscope" technique in the context of an ongoing T-cell immune reconstitution. Secondary ADs are increasingly recognized after HSCT for AD. In our case, development of myasthenia followed clonal T-cell expansion. Detailed T-cell repertoire analysis may shed light on autoreactivity mechanisms after HSCT and may help to identify patients at risk

Thymic function recovery after unrelated donor cord blood or T-cell depleted HLA-haploidentical stem cell transplantation correlates with leukemia relapse

Use of alternative donors/sources of hematopoietic stem cells (HSC), such as cord blood (CB) or HLA-haploidentical (Haplo)-related donors, is associated with a significant delay in immune reconstitution after transplantation. Long-term T-cell immune reconstitution largely relies on the generation of new T cells in the recipient thymus, which can be evaluated through signal joint (sj) and beta T-cell-Receptor Excision Circles (TREC) quantification. We studied two groups of 33 and 24 children receiving, respectively, HSC Transplantation (HSCT) from an HLA-haploidentical family donor or an unrelated CB donor, for both malignant (46) and non-malignant disorders (11). Relative and absolute sj and beta-TREC values indicated comparable thymic function reconstitution at 3 and 6 months after the allograft in both groups. Compared to children with non-malignant disorders, those with hematological malignancies had significantly lower pre-transplantation TREC counts. Patients who relapsed after HSCT had a significantly less efficient thymic function both before and 6 months after HSCT with especially low beta-TREC values, this finding suggesting an impact of early intra-thymic T-cell differentiation on the occurrence of leukemia relapse

Long-term immune reconstitution and T cell repertoire analysis after autologous hematopoietic stem cell transplantation in systemic sclerosis patients

International audienceThe determinants of clinical responses after autologous hematopoietic stem cell transplantation (aHSCT) in systemic sclerosis (SSc) are still unraveled. We analyzed long-term immune reconstitution (IR) and T cell receptor (TCR) repertoire diversity in 10 SSc patients, with at least 6 years simultaneous clinical and immunological follow-up after aHSCT. Patients were retrospectively classified as long-term responders (A, n = 5) or non-responders (B, n = 5), using modified Rodnan's skin score (mRSS) and forced vital capacity (FVC%). All patients had similar severe SSc before aHSCT. Number of reinjected CD34 + cells was higher in group B versus A (P = 0.02). Long-term mRSS fall >25% was more pronounced in group A (P = 0.004), the only to improve long-term FVC% >10% (P = 0.026). There was an overall trend toward increased of T cell reconstitution in group B versus A. B cells had a positive linear regression slope in group A (LRS = 11.1) and negative in group B (LRS = −11.6). TCR repertoire was disturbed before aHSCT and the percentage of polyclonal families significantly increased at long-term (P = 0.046), with no difference between groups. Despite improved skin score after aHSCT in all SSc patients, pretransplant B cell clonal expansion and faster post-transplant T cell IR in long-term non-responder/relapsing patients call for new therapeutic protocols guided by IR analysis to improve their outcome

Combinations of Spok genes create multiple meiotic drivers in Podospora

Meiotic drive is the preferential transmission of a particular allele during sexual reproduction. The phenomenon is observed as spore killing in multiple fungi. In natural populations of Podospora anserina, seven spore killer types (Psks) have been identified through classical genetic analyses. Here we show that the Spok gene family underlies the Psks. The combination of Spok genes at different chromosomal locations defines the spore killer types and creates a killing hierarchy within a population. We identify two novel Spok homologs located within a large (74-167 kbp) region (the Spok block) that resides in different chromosomal locations in different strains. We confirm that the SPOK protein performs both killing and resistance functions and show that these activities are dependent on distinct domains, a predicted nuclease and kinase domain. Genomic and phylogenetic analyses across ascomycetes suggest that the Spok genes disperse through cross-species transfer, and evolve by duplication and diversification within lineages