Mechanism of Chimeric Vaccine Mediated Immune Suppression of Human Dendritic Cells

Type 1 diabetes mellitus is a chronic inflammatory disease in which insulin producing β-cells of the pancreatic islets are killed by autoreactive cells of the immune system in response to a loss of tolerance. Dendritic cells (DC) interact predominantly with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this dissertation, immature human dendritic cells (iDC) were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS). Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1) shown to be directly linked to CTB-INS-induced DC activation and maturation. Treatment of vaccinated DCs with the pharmacological NF-κB inhibitors ACHP or DHMEQ inhibited IDO1 biosynthesis, suggesting a role for NF-κB signaling in CTB-INS vaccine up-regulation of dendritic cell IDO1. Further, blocking the NF-κB-inducing kinase (NIK) phosphorylation of IKK-α dimers and translocation of p52/RelB complexes to the nucleus with anti-NIK siRNA, significantly inhibited IDO1 expression in human DCs. Chromatin immunoprecipitation (ChIP) analysis, showed that RelB-p52 dimers bound dendritic cell NF-κB consensus sequences in the IDO1 promoter region, demonstrating vaccine stimulation of NF-κB non-canonical pathway activation of IDO1 expression in human DCs in vivo. Addition of the Tumor Necrosis Factor Associated Factors (TRAF) TRAF6 and TRAF 2, 3 blocking peptides to vaccinated DCs dramatically reduced the level of IDO1 biosynthesis and stimulated DC suggesting the vaccine may function in the same signaling pathway as TNFR super-family for the up-regulation of IDO1 biosynthesis in vaccinated dendritic cells. Together, these data confirm CTB-INS vaccine activation of the non-canonical NF-κB signaling pathway TNFR receptor family up-regulation of dendritic cell IDO1 biosynthesis permitting vaccine inhibition of DC maturation leading to the suppression of type 1 diabetes development

Langues camerounaises et identité : le drame linguistico-culturel des valeurs traditionnelles : le cas de la famille, l’éducation et la société chez les Banen

Résumé : La langue constitue le tout premier trait identitaire de tout individu ou toute société. Ainsi, dans les pays développés, des initiatives de développement et de promotion telles que l’académie française en France, Institute für die deutsche Sprache en Allemagne concourent au quotidien au rayonnement de leur langue. Au Cameroun, de telles initiatives privées sont menées par l’ANACLAC, la SIL ou la CABTAL regroupant les différents comités de langue ou travaillant avec différentes langues nationales ; celles-ci subissent non seulement les affres des langues officielles dominantes, qui sont un instrument d’instruction moins indiqué que celui que possède l’enfant de sa naissance (Cheikh Anta Diop 1990, p. 35), mais aussi les revers de la puissance de développement technologique, qui a soumis les pays en voie de développement dans une course folle de vouloir réduire l’écart, mais sans issue. Ce qui a fait passer l’Afrique du statut de l’oralité primitive à l’écrit aliénant, de la diversité linguistique à un monolinguisme étatique[1], de ses valeurs primitives ancestrales à sa civilité colorée. Cette mutation est une sorte de cataclysme qui a touché l’âme même des Africains à savoir la famille, l’éducation et la société toute entière cherchant à les mettre ‘upside down’ (sens dessous-dessus). La notion de drame linguistico-culturel renvoie au concept de ‘language shift’ de Fasold (1984 :213) qu’il qualifie de « Language shift simply means that a community gives up a language completely in favor of anaother one » et par extension pour ce qui nous concerne, l’abandon de la langue et la culture Banen au profit du français. La présente communication se propose de faire un examen de conscience à l’aide de ces concepts qui sont tous des institutions de promotion des langues et des cultures de chaque peuple et en s’appuyant sur l’approche ethnométhodologique et surtout grâce à l’usage paraméologique. Mots-clés : langues camerounaises, identité, culture, famille, écol

Prevalence of HIV, HBV and Chlamydia infections in Cameroonian University context: case of the University of Dschang, in the Western Region

Introduction: In sub-Saharan Africa HIV infection remains largely epidemic, whereas HBV infection is highly endemic (>8%). In Cameroon, HIV prevalence is 4.3%. Concerning HBV and chlamydia infections, their prevalence are both ≥10%. Young adults, including university students, are the population groups mostly affected. Epidemiological data on these infections, among university students could be helpful to implement specific prevention strategies. Methods: A descriptive study was performed in May 2013 among 624 students from the University of Dschang, Cameroon. Participants were screened for HIV, HBV and Chlamydia infections. Data was collected by a standard questionnaire and analyzed by Epi Info. Results: Average age of participants was 23.3 years (σ = 3.2) with female predominance (58.7%). Prevalence of HIV, HBV and Chlamydia infection was 1.1% (7/624), 2.8% (5/176) and 2.0% (2/100) respectively. 83.2% of participants were sexually active. Concerning sexual risk behaviors, participants reported having multi partners (14.8%), using condom occasionally (58.6%) or never (5.0%). 100%, 62.6% and 52.2% reported to be aware on HIV, HBV and Chlamydia infections respectively. In addition, only 5.5% and 21.3% of the participants were aware of their HBV and Chlamydia status respectively, versus 64.4% for HIV. The excessive cost of HBV and Chlamydia tests has been identified as the major barrier to testing (87.6%). Conclusion: Among college Cameroonian students the prevalence of HIV, HBV and Chlamydia infections seems to be relatively low if compared to general population. However, having multiple sexual partners in addition to non-systematic use of condoms during sexual intercourse represents risk behaviors among students. Awareness campaigns and screening facilitation on HBV and chlamydia infections need to be strengthened

Reversal of New Onset Type 1 Diabetes by Oral Salmonella-Based Combination Therapy and Mediated by Regulatory T-Cells in NOD Mice

Autoimmune diseases such as type 1 diabetes (T1D) involve the loss of regulatory mechanisms resulting in increased tissue-specific cytotoxicity. The result is destruction of pancreatic insulin-producing β-cells and loss of glucose homeostasis. We are developing a novel oral vaccine using live attenuated Salmonella to deliver TGFβ, IL10, and the diabetic autoantigen preproinsulin combined with low-doses of anti-CD3 mAb. Here we show that oral administration of Salmonella-based anti-CD3 mAb combined therapy reverses new-onset T1D in non-obese diabetic (NOD) mice. The therapeutic effect of the combined therapy was associated with induction of immune suppressive CD4+CD25+Foxp3+ Treg and CD4+CD49b+LAG3+ Tr1 cells. In adoptive transfer experiments, adding or depleting Treg or Tr1 cells indicated that both are important for preventing diabetes in combined therapy-treated mice, but that Tr1 cells may have a more central role. Furthermore, induced Tr1 cells were found to be antigen-specific responding to peptide stimulation by secreting tolerance inducing IL10. These preclinical data demonstrate a role for Treg and Tr1 cells in combined therapy-mediated induction of tolerance in NOD mice. These results also demonstrate the potential of oral Salmonella-based combined therapy in the treatment of early T1D

Fibroblast cell-based therapy prevents induction of alopecia areata in an experimental model

YesAlopecia areata (AA) is an autoimmune hair loss disease with infiltration of proinflammatory cells into hair follicles. Current therapeutic regimens are unsatisfactory mainly because of the potential for side effects and/or limited efficacy. Here we report that cultured, transduced fibroblasts, which express the immunomodulatory molecule indoleamine 2,3-dioxygenase (IDO), can be applied to prevent hair loss in an experimental AA model. A single intraperitoneal (IP) injection of IDO-expressing primary dermal fibroblasts was given to C3H/HeJ mice at the time of AA induction. While 60–70% of mice that received either control fibroblasts or vehicle injections developed extensive AA, none of the IDO-expressing fibroblast-treated mice showed new hair loss up to 20 weeks post injection. IDO cell therapy significantly reduced infiltration of CD4+ and CD8+ T cells into hair follicles and resulted in decreased expression of TNF-α, IFN-γ and IL-17 in the skin. Skin draining lymph nodes of IDO fibroblast-treated mice were significantly smaller, with more CD4+ CD25+ FoxP3+ regulatory T cells and fewer Th17 cells than those of control fibroblast and vehicle-injected mice. These findings indicate that IP injected IDO-expressing dermal fibroblasts can control inflammation and thereby prevent AA hair loss.Canadian Institutes of Health Researches (Funding Reference Number: 134214 and 136945)

Crosstalk Between Innate and T Cell Adaptive Immunity With(in) the Muscle

Growing evidence demonstrates a continuous interaction between the immune system and the skeletal muscle in inflammatory diseases of different pathogenetic origins, in dystrophic conditions such as Duchenne Muscular Dystrophy as well as during normal muscle regeneration. Although one component of the innate immunity, the macrophage, has been extensively studied both in disease conditions and during cell or gene therapy strategies aiming at restoring muscular functions, much less is known about dendritic cells and their primary immunological targets, the T lymphocytes. This review will focus on the dendritic cells and T lymphocytes (including effector and regulatory T-cells), emphasizing the potential cross talk between these cell types and their influence on the structure and function of skeletal muscle