Prevalencia y concentración de Porphyromonas gingivalis en fluido crevicular y saliva de pacientes diabéticos

30 p.El estado periodontal de un paciente puede verse afectado por factores como la microbiota supra y subgingival, factores ambientales y las respuestas inmunes e inflamatorias del huésped. Pudiendo pasar de un estado de salud periodontal a un estado de enfermedad periodontal. Dentro de los factores ambientales que influyen en el desarrollo de la enfermedad periodontal podemos encontrar la Diabetes Mellitus, la cual forma parte de las enfermedades crónicas más comunes en la población, teniendo ésta una relación bidireccional con la enfermedad periodontal, pudiendo ayudar a su progresión. Cuando nos referimos a los factores microbianos, cobra importancia la formación del biofilm subgingival, dentro del cual destaca la Porphyromonas gingivalis (P. gingivalis), la cual se presenta en alta frecuencia en pacientes con enfermedad periodontal, provocando un aumento en la inflamación y destrucción del epitelio y tejido conectivo. Este estudio tiene por objetivo establecer si existen diferencias en la prevalencia y concentración de P. gingivalis presente en los pacientes diabéticos compensados y no compensados en base a los índices periodontales, usuarios del Centro de Salud Familiar (CESFAM) Villa Magisterio de Talca. Esto mediante la toma de muestras de fluido crevicular, de surco o saco periodontal, y saliva, con el fin de determinar una relación entre P. gingivalis y el control glicémico. Sobre la P. gingivalis existe una alta prevalencia y diferencias de concentración en pacientes diabéticos compensados y no compensados, no significativas. Palabras clave: Enfermedad periodontal, Porphyromonas gingivalis, Diabetes mellitus tipo II, Hemoglobina glicosilad

IRGM Is a Common Target of RNA Viruses that Subvert the Autophagy Network

Autophagy is a conserved degradative pathway used as a host defense mechanism against intracellular pathogens. However, several viruses can evade or subvert autophagy to insure their own replication. Nevertheless, the molecular details of viral interaction with autophagy remain largely unknown. We have determined the ability of 83 proteins of several families of RNA viruses (Paramyxoviridae, Flaviviridae, Orthomyxoviridae, Retroviridae and Togaviridae), to interact with 44 human autophagy-associated proteins using yeast two-hybrid and bioinformatic analysis. We found that the autophagy network is highly targeted by RNA viruses. Although central to autophagy, targeted proteins have also a high number of connections with proteins of other cellular functions. Interestingly, immunity-associated GTPase family M (IRGM), the most targeted protein, was found to interact with the autophagy-associated proteins ATG5, ATG10, MAP1CL3C and SH3GLB1. Strikingly, reduction of IRGM expression using small interfering RNA impairs both Measles virus (MeV), Hepatitis C virus (HCV) and human immunodeficiency virus-1 (HIV-1)-induced autophagy and viral particle production. Moreover we found that the expression of IRGM-interacting MeV-C, HCV-NS3 or HIV-NEF proteins per se is sufficient to induce autophagy, through an IRGM dependent pathway. Our work reveals an unexpected role of IRGM in virus-induced autophagy and suggests that several different families of RNA viruses may use common strategies to manipulate autophagy to improve viral infectivity

Cutting edge: abortive proliferation of CD46-induced Tr1-like cells due to a defective Akt/Survivin signaling pathway.

T regulatory cell 1 (Tr1) are low proliferating peripherally induced suppressive T cells. Engaging CD3 and CD46 on human CD4+ T cells induces a Tr1-like phenotype. In this study, we report that human Tr1-like cells do not sustain proliferation over time. The weak proliferation of these cells results first from their inability to sustain expression of various cell cycle-associated proteins, to efficiently degrade the inhibitor of cell cycle progression p27/Kip1 and, as a consequence, in their accumulation in the G0-G1 phase. Also, the reduced proliferation of Tr1-like cells results from their increased sensitivity to death as they divide, through a mechanism that is neither Fas-mediated nor Bcl2/Bcl-xL related. Both properties, impaired cell cycle and death sensitivity, are explained by a specific defective activation of Akt that impairs the expression of Survivin. Thus, our results show that CD3/CD46-induced Tr1-like cells die through a process of abortive proliferation

CD40 signaling in human dendritic cells is initiated within membrane rafts

Despite CD40’s role in stimulating dendritic cells (DCs) for efficient specific T-cell stimulation, its signal transduction components in DCs are still poorly documented. We show that CD40 receptors on human monocyte-derived DCs associate with sphingolipid- and cholesterol-rich plasma membrane microdomains, termed membrane rafts. Following engagement, CD40 utilizes membrane raft-associated Lyn Src family kinase, and possibly other raft-associated Src family kinases, to initiate tyrosine phosphorylation of intracellular substrates. CD40 engagement also leads to a membrane raft-restricted recruitment of tumor necrosis factor (TNF) receptor-associated factor (TRAF) 3 and, to a lesser extent, TRAF2, to CD40’s cytoplasmic tail. Thus, the membrane raft structure plays an integral role in proximal events of CD40 signaling in DCs. We demonstrate that stimulation of Src family kinase within membrane rafts initiates a pathway implicating ERK activation, which leads to interleukin (IL)-1α/β and IL-1Ra mRNA production and contributes to p38-dependent IL-12 mRNA production. These results provide the first evidence that membrane rafts play a critical role in initiation of CD40 signaling in DCs, and delineate the outcome of CD40-mediated pathways on cytokine production

Autophagy Receptor NDP52 Regulates Pathogen-Containing Autophagosome Maturation.

Affiliations ECOFECTInternational audienceXenophagy, an essential anti-microbial cell-autonomous mechanism, relies on the ability of the autophagic process to selectively entrap intracellular pathogens within autophagosomes to degrade them in autolysosomes. This selective targeting is carried out by specialized autophagy receptors, such as NDP52, but it is unknown whether the fusion of pathogen-containing autophagosomes with lysosomes is also regulated by pathogen-specific cellular factors. Here, we show that NDP52 also promotes the maturation of autophagosomes via its interaction with LC3A, LC3B, and/or GABARAPL2 through a distinct LC3-interacting region, and with MYOSIN VI. During Salmonella Typhimurium infection, the regulatory function of NDP52 in autophagosome maturation is complementary but independent of its function in pathogen targeting to autophagosomes, which relies on the interaction with LC3C. Thus, complete xenophagy is selectively regulated by a single autophagy receptor, which initially orchestrates bacteria targeting to autophagosomes and subsequently ensures pathogen degradation by regulating pathogen-containing autophagosome maturation