Publications (4)18.14 Total impact
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Article: Loss of mucosal CD103+ DCs and IL-17+ and IL-22+ lymphocytes is associated with mucosal damage in SIV infection.
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ABSTRACT: Human immunodeficiency virus (HIV) and Simian immunodeficiency virus (SIV) disease progression is associated with multifocal damage to the gastrointestinal tract epithelial barrier that correlates with microbial translocation and persistent pathological immune activation, but the underlying mechanisms remain unclear. Investigating alterations in mucosal immunity during SIV infection, we found that damage to the colonic epithelial barrier was associated with loss of multiple lineages of interleukin (IL)-17-producing lymphocytes, cells that microarray analysis showed expressed genes important for enterocyte homeostasis, including IL-22. IL-22-producing lymphocytes were also lost after SIV infection. Potentially explaining coordinate loss of these distinct populations, we also observed loss of CD103+ dendritic cells (DCs) after SIV infection, which associated with the loss of IL-17- and IL-22-producing lymphocytes. CD103+ DCs expressed genes associated with promotion of IL-17/IL-22+ cells, and coculture of CD103+ DCs and naïve T cells led to increased IL17A and RORc expression in differentiating T cells. These results reveal complex interactions between mucosal immune cell subsets providing potential mechanistic insights into mechanisms of mucosal immune dysregulation during HIV/SIV infection, and offer hints for development of novel therapeutic strategies to address this aspect of AIDS virus pathogenesis.Mucosal Immunology 05/2012; 5(6):646-57. · 6.96 Impact Factor -
Article: Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections
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ABSTRACT: The chronic phase of HIV infection is marked by pathological activation of the immune system, the extent of which better predicts disease progression than either plasma viral load or CD4(+) T cell count. Recently, translocation of microbial products from the gastrointestinal tract has been proposed as an underlying cause of this immune activation, based on indirect evidence including the detection of microbial products and specific immune responses in the plasma of chronically HIV-infected humans or SIV-infected Asian macaques. We analyzed tissues from SIV-infected rhesus macaques (RMs) to provide direct in situ evidence for translocation of microbial constituents from the lumen of the intestine into the lamina propria and to draining and peripheral lymph nodes and liver, accompanied by local immune responses in affected tissues. In chronically SIV-infected RMs this translocation is associated with breakdown of the integrity of the epithelial barrier of the gastrointestinal (GI) tract and apparent inability of lamina propria macrophages to effectively phagocytose translocated microbial constituents. By contrast, in the chronic phase of SIV infection in sooty mangabeys, we found no evidence of epithelial barrier breakdown, no increased microbial translocation and no pathological immune activation. Because immune activation is characteristic of the chronic phase of progressive HIV/SIV infections, these findings suggest that increased microbial translocation from the GI tract, in excess of capacity to clear the translocated microbial constituents, helps drive pathological immune activation. Novel therapeutic approaches to inhibit microbial translocation and/or attenuate chronic immune activation in HIV-infected individuals may complement treatments aimed at direct suppression of viral replicationPLoS Pathog. 01/2010; 6(8). -
Article: Progress in the molecular diagnosis of facioscapulohumeral muscular dystrophy and correlation between the number of KpnI repeats at the 4q35 locus and clinical phenotype
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ABSTRACT: Genotype analysis by using the p13E-11 probe and other 4q35 polymorphic markers was performed in 122 Italian facioscapulohumeral muscular dystrophy families and 230 normal controls. EcoRI—BlnI double digestion was routinely used to avoid the interference of small EcoRI fragments of 10qter origin that were found in 15% of the controls. An EcoRI fragment ranging between 10 and 28 kb that was resistant to BlnI digestion was detected in 114 of 122 families (93%) comprising 76 familial and 38 isolated cases. Among the unaffected individuals, 3 were somatic mosaics and 7, carrying an EcoRI fragment larger than 20 kb, could be rated as nonpenetrant gene carriers. In a cohort of 165 patients with facioscapulohumeral muscular dystrophy we found an inverse correlation between fragment size and clinical severity. A severe lower limb involvement was observed in 100% of patients with an EcoRI fragment size of 10 to 13 kb (1–2 KpnI repeats left), in 53% of patients with a fragment size of 16 to 20 kb (3–4 KpnI repeats left), and in 19% of patients with a fragment size larger than 21 kb (>4 KpnI repeats left). Our results confirm that the size of the fragment is a major factor in determining the facioscapulohumeral muscular dystrophy phenotype and that it has an impact on clinical prognosis and genetic counseling of the disease. Ann Neurol 1999;45:751–757Annals of Neurology 05/1999; 45(6):751 - 757. · 11.09 Impact Factor -
Article: Diagnostic des adénopathies malignes au moyen de l’aspiration à l’aiguille fine écho-guidée par ultrasonographie endoscopique
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ABSTRACT: 1) L’exactitude diagnostique de l’AAF guidée par l’USE est de 100 % pour le diagnostic de l’extension métastatique des ganglions médiastinaux, péripancréatiques et du tronc cœliaque. 2) Cet acte diagnostique est sans danger. 3) Une AAF positive pour les ganglions métastatiques de patients porteurs d’un cancer œsophagien, pancréatique ou pulmonaire fournit des informations cliniques utiles pour décider de l’abstention de tout traitement chirurgical coûteux et inutile. 1. The accuracy of EUS + FNA was 100 % in determining metastatic spread to lymph nodes in the mediastinum, celiac axis and the peripancreatic area. 2. The procedure was safe. 3. A positive FNA for LN metastases in patients with esophageal, pancreatic and lung cancer provided clinically useful information which helped decide against surgery and thus may provide cost savings.Acta Endoscopica 08/1995; 25(5):473-474. · 0.09 Impact Factor
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- Acta Endoscopica (1)
- Annals of Neurology (1)
- Mucosal Immunology (1)
