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P. falciparum soluble extracts potentiate the suppressive function of polyclonal Treg cells through activation of TGFβ-mediated signals.

Cirelli, Domenico
Fonte: La Sapienza Universidade de Roma Publicador: La Sapienza Universidade de Roma
Tipo: Tese de Doutorado
EN
Relevância na Pesquisa
96.37%
Increased numbers of T regulatory cells (Tregs), key mediators of immune homeostasis, were reported in human and murine malaria and it is current opinion that these cells play a role in balancing protective immunity and pathogenesis during infection. However, the mechanisms governing their expansion during malaria infection are not completely defined. In this article we show that soluble extracts of Plasmodium falciparum (PfSEs), but not equivalent preparation of uninfected erythrocytes, induce the differentiation of polyclonally activated CD4(+) cells in Tregs endowed with strong suppressive activity. PfSEs activate latent TGFβ bound on the membrane of Treg cells, thus allowing the cytokine interaction with TGFβ receptor, and inducing Foxp3 gene expression and TGFβ production. The activation of membrane-bound latent TGFβ by PfSEs is significantly reduced by a broad-spectrum metalloproteinases inhibitor with Zn(++) -chelating activity, and completely inhibited by the combined action of such inhibitor and antibodies to a P. falciparum thrombospondin-related adhesive protein (PfTRAP). We conclude that Pf-Zn(++) -dependent proteinases and, to a lesser extent, PfTRAP molecules are involved in the activation of latent TGFβ bound on the membrane of activated Treg cells and suggest that...

New insights into the pathogenesis and treatment of chlamydial infections

DE SANTIS, FIORENZO
Fonte: La Sapienza Universidade de Roma Publicador: La Sapienza Universidade de Roma
Tipo: Tese de Doutorado
EN
Relevância na Pesquisa
96.07%
Chlamydiae are obligate intracellular Gram-negative bacteria with a unique biphasic developmental cycle, alternating between infectious elementary bodies and replicative reticulate bodies. However, when exposed to stressful conditions such as iron deprivation and IFN-gamma exposure, they fail to complete their developmental cycle generating morphologically aberrant reticulate bodies called persistent forms, which remain viable but non-infectious inside the host-cell for a long time and are difficult to eradicate with antibiotics. Chlamydiae cause a broad spectrum of diseases. Chlamydia pneumoniae causes community-acquired pneumonia and other respiratory tract infections, while Chlamydia trachomatis is the leading cause of sexually transmitted diseases all over the world and of trachoma in developing countries. More importantly, these pathogens may cause chronic sequelae. In fact, C. pneumoniae infections may be associated to atherosclerosis, whereas C. trachomatis infections lead to ectopic pregnancy, obstructive infertility and reactive arthritis. These sequelae could result from the inflammatory state induced by the persistent forms. In our research, we studied in vitro different aspects of chlamydial pathogenesis and treatment in C. pneumoniae and C. trachomatis...

Membrane-active derivatives of the frog skin peptide Esculentin-1 against relevant human pathogens

LUCA, VINCENZO
Fonte: La Sapienza Universidade de Roma Publicador: La Sapienza Universidade de Roma
Tipo: Tese de Doutorado
EN
Relevância na Pesquisa
46.58%
Candida albicans represents one of the most prevalent species causing life-threatening fungal infections. Current treatments to defeat Candida albicans have become quite difficult, due to their toxic side effects and the emergence of resistant strains. Antimicrobial peptides (AMPs) are fascinating molecules with a potential role as novel anti-infective agents. However, only a few studies have been performed on their efficacy towards the most virulent hyphal phenotype of this pathogen. The purpose of this work is to evaluate the anti-Candida activity of the N-terminal 1–18 fragment of the frog skin AMP esculentin- 1b, Esc(1–18), under both in vitro and in vivo conditions using Caenorhabditis elegans as a simple host model for microbial infections. Our results demonstrate that Esc(1–18) caused a rapid reduction in the number of viable yeast cells and killing of the hyphal population. Esc(1–18)revealed a membrane perturbing effect which is likely the basis of its mode of action. Esc(1-18) is able (1) to kill both growing stages of Candida; (2) to promote survival of Candida-infected living organisms and (3) to inhibit transition of these fungal cells from the roundish yeast shape to the more dangerous hyphal form at sub-inhibitory concentrations. Pseudomonas aeruginosa is an opportunistic bacterial pathogen that forms sessile communities...

IL VIRUS DELLA SINDROME ACUTA RESPIRATORIA SEVERA E IL SISTEMA INTERFERON: CAPACITA' DI INDUZIONE ED ATTIVITA' ANTIVIRALE

Scagnolari, Carolina
Fonte: La Sapienza Publicador: La Sapienza
Tipo: Tese de Doutorado
IT
Relevância na Pesquisa
106.08%
Faggioni, Alberto Paolini, Rossella Aglianò, Anna Maria