Archives de l'Institut Pasteur de Tunis最新文献

A sero-epidemiological study was carried out on 5660 sera collected, between 2006 and 2008, from different flocks in different regions of the country. The ELISA results showed low levels of antibodies indicating vaccination failures. 45 to 69% of the flocks showed positive levels of antibodies and only 5 to 15% of these were protected. The pathogenicity studies of the Tunisian field isolates TN20/00 and TN335/01 demonstrated high clinical and lesion scores indicating the pathogenic effect of the two isolates. The challenge experiments conducted to evaluate the cross-protection between the H120 vaccine and the field isolates showed low protection rate, especially against the TN20/00 virus. The overall results allowed the determination of the pathogenic nature of the field isolates and a vaccination program based on the use of the only Massachusetts H120 strain did not reduce tracheal and kidney lesions. To better control the disease, adapting the vaccination program by using vaccine allowing better protection against variant strains, is recommended.

Different works of DNA based vaccination against leishmaniasis highlight the complexity of the induced immune responses to fight against the disease. In this work, we exploited the capacity of IL-12 and GMC-SF to activate immune cell mediators and effectors to induce a Th1 response, more capable of clearing the parasite. To generate these immunomodulating activities, we associated eukaryotic expressing vectors of murine IL-12 and GMC-SF to several DNA based vaccine candidates encoding to several L. (L.) major antigens, in the BALB/c mouse. When mice were challenged with a high parasitic load in the hind footpad, no additional protective effect could be generated. However, when the challenge was carried out in the inner face of the ear with a small parasitic load, the association of plasmids encoding to IL-12 and GMC-SF to DNA based vaccination, the protective effects were increased.

To investigate a possible association between functional polymorphisms of the protein tyrosine phosphatase nonreceptor type 22 (PTPN22-R620W) and receptors for the Fc fragment of IgG (FcgRIIa-H131R, FcgRIIIa-F158V FcgRIIIb-NA1/NA2), and rheumatoid arthritis (RA), 133 Tunisian patients with RA and 100 controls were genotyped. We found strong evidence of an association of PTPN22 620W allele and RA. However, analysis does not detect an association between auto-antibodies seropositivity, presence of nodules or erosions and this allele. No significant skewing of any of the three FcgR polymorphisms was seen in this RA group. Nevertheless, we identified FcgRIIIa-V/V158 as the most important FcgR genotype for severe disease subset with joint erosions and observed that patients with FcgRIIIb-NA2/NA2 genotype had an earlier incidence of clinical symptoms. In conclusion, we have confirmed that PTPN22 620W allele is associated with Tunisian RA but does not constitute a factor influencing clinical manifestations. Conversely, this study supports that the FcgRIIa/IIIa and IIIb polymorphisms could influence the course and the severity of this disease. A large number of samples are required to provide independent confirmation of these findings.

The hepatitis C virus (HCV) is the principal agent of viral chronic hepatitis. Cirrhosis and hepatocellular carcinoma are the major complications of this chronic infection. In haemodialysis, HCV infection remains a very frequent problem. Several autoimmune phenomena have been described during this infection. Two hundred haemodialysis patients, all of them anti-HCV (+), were included in this study to evaluate the frequency of Anti-Nuclear Autoantibodies (ANA), anti-cardiolipine antibodies (ACL), anti-smooth muscle antibodies (ASMA), anti-mitochondria antibodies (AMA), anti-thyroperoxydase antibodies (ATPO) and Rheumatoid Factor (RF) comparing them to healthy controls. Sixty eight serums (34%) patients were positive to at least one of the auto-antibodies tested. The difference between patients and controls was statistically significant. These markers were dominated by RF of the IgM isotype and ACL of the IgG isotype. Nevertheless, the positivity of ANA, ASMA, AMA and ATPO was not statistically different comparing to the controls. In addition, an association between the presence of the auto-antibodies and the viral replication was found suggesting that HCV is responsible for inducing these autoimmune phenomena.

HLA-G is a particular non classical HLA class I molecule. Despite its tissue-restricted expression and low polymorphism, this molecule plays an important role in innate and adaptative immunity. The tolerogenic propriety of HLA-G makes it an immunomodulatory molecule acting in the early phases of conception, protecting fetal tissues from the maternal immune system. Immunomodulatory functions of HLA-G and the associations of this molecule with some pathological states are reported in this review. So, little amounts of soluble HLA-G or particular allelic expression of this molecule are associated with some pregnancy complications. HLA-G expression on tumor cells by preventing antitumor responses via a trogocytosis mechanism and regulatory T cells induction is associated with invasiveness and clinical evolution of some tumor types. HLA-G is also involved in the protection of the transplanted tissues from rejection. Revealing of new more functional homomultimeric isoforms of this molecule offers new insight in a better understanding of clinical and biological role of HLA-G.

The aim of the study was to assess hepatitis A virus (HAV) seroprevalence in blood donors from South Tunisia in two periods 2000 and 2007. Serum samples collected from 376 blood donors in each period aged 18 to 30 years from different regions of South Tunisia were analysed for anti-HAV IgG. The global seroprevalence of HAV infection was 85.9% in 2007 as compared with 94.9% in 2000. The seroprevalence in the 18-20 years age group was 91.9% in 2000 vs 80.6% in 2007, and increased to 99% in 2000 and 92% in 2007 in the subjects over 26. Taking account of geographic area, the HAV seroprevalence in Sfax city decreased from 88.9% in 2000 to 62.7% in 2007 (p < 0.001), but it is still approximatively the same in rural areas (98.4% and 96%) and in the governorates of South Tunisia (97.6% and 99.2%). In conclusion, the number of adults in the city of Sfax which are not immunized against HAV is increasing. Thus, adolescents and young adults are at risk to develop symptomatic and potentially severe hepatitis A.

Mitochondria are the intracellular organelle responsible for the production of cellular energy. They play an important role in the regulation of cellular metabolism, apoptosis and oxydative stress control. Mitochondrial DNA (mtDNA) has many special features such as a high copy number in cell, maternal inheritance, and a high mutation rate which have made it attractive to scientists from many fields. In anthropological genetics, mtDNA is useful to trace geographic distribution of genetic variation, for the investigation of expansions, migrations and other pattern of gene flow. mtDNA is widely applicated in forensic science. It is a powerful implement to identify human remains. mtDNA is characterized by the high rate of polymorphisms and mutations. Some of which are increasingly recognized as an important cause of human pathology such as oxidative phosphorylation (OXPHOS) disorders, maternally inherited diabetes and deafness (MIDD), Type 2 diabetes mellitus, neurodegenerative disorders, heart failure and cancer.

Bleomycins are a family of glycopeptides isolated from streptomyces verticillus and exhibiting antibiotic properties. They are commonly included in chemotherapy regimens used to treat patients with Hodgkin's or non Hodgkin's malignant lymphoma, squamous-cell carcinoma or germ-cell tumor. The chemical structure and action mode of bleomycin have been extensively studied, in contrast, the molecular mechanisms of the cytotoxic effects of bleomycin, in vivo, remain poorly understood. Recently, the apoptotics signaling pathway induce by bleomycin was the object of study, of many groups. In this sense, some studies suggested that bleomycin induce in some cells different apoptotic pathway in dose and time depending manner. The sensibility or the resistance to apoptosis induced by bleomycin may explain the sensibility or the resistance of tumor cells to bleomycin. The aim of this review was to describe the machinery of apoptosis induced by bleomycin in tumor cells.

The lactococcin B (LnB) is a hydrophobic, positively charged bacteriocin, produced by Lactococcus lactis ssp. cremoris 9B4. It consists of a peptidic chain made up of 47 amino acid residues, and inhibits Lactococcus exclusively. In order to study its biological activity a synthetic lactococcin B (LnBs) was obtained by solid-phase chemical synthesis using a Fmoc strategy. LnBs was shown to be indistinguishable from the natural peptide. In addition, a synthetic (7-47) LnBst analogue was obtained by withdrawal of peptidyl-resin after the 41 cycle of LnBs peptide chain assembly. The synthetic N-terminal truncated (7-47) LnBst analogue was found to be inactive on indicator strains. Our results strongly suggest that the first six N-terminal amino acid residues are involved in the bactericidal activity of LnB.

Leishmania infantum (L.i) is responsible for visceral (VL) or cutaneous (CL) leishmaniasis. Previous studies done in Honduras by differential display reverse transcriptase-polymerase chain reaction (DDRT-PCR) failed to demonstrate differences in expression profiles among L. infantum VL and CL parasites. For purpose of comparing expression among L. infantum isolates in Tunisia, a variant of this technique adapted from a commercial kit was developed involving pairs of random and anchored mini-exon primers for isolation and identification of differentially displayed cDNAs. To assess the efficiency of this variant, 34 pairs were applied to 2 consecutive dilutions of cDNAs from promastigotes at end of in vitro exponential growth of 2 visceral (LV50) and cutaneous (DREP14) isolates from Tunisia, thus increasing chance for observing differences among the cDNAs. Profiles were compared and analyzed as regards number and phenotype of bands displayed in 4 types of highly similar amplification profiles among the 2 cDNAs; 26 primer pair combinations generated in total 6.8% differentially displayed bands that had variable intensities or were present/absent, in comparable proportions in the 2 isolates. Analysis further demonstrated differences in amplification efficiency of some primers, emphasizing on qualitative and quantitative impact of relative proximity of the priming sites. Nine present/absent bands were cloned, sequenced and analyzed in silico. Mismatches at priming sites seem to underlie amplification of such bands. Only five products could be referred to annotated gene. Among the genes identified, we list histone H4, largely known to be differentially expressed among L.i stages, and "NTF2-like" for which overexpression in one cDNA was here confirmed. To conclude, the variant developed could be used further in Leishmania expression analysis with appropriate cautions about false positives.