Modulation of the innate immune response by Yersinia enterocolitica upon systemic infection

Matteoli, Gianluca (2006) Modulation of the innate immune response by Yersinia enterocolitica upon systemic infection. [Tesi di dottorato] (Inedito)

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Abstract

Yersinia enterocolitica causes acute and chronic enteric infections and complications such as septicaemia or reactive arthritis. The survival strategy of Y. enterocolitica in hosts is to silence the innate immune as well as the adaptive immune response. For this purpose Y. enterocolitica has developed a Type III secretion system which allows to directly translocate six effectors proteins Yops (Yersinia outer protein H, T, O, P, M and E) into host cells. Aim of this work was the characterization of the molecular mechanisms by which the Yops affect gene expression in cells of the innate immune response, in vivo. For this purpose, CD11b+ cells, including macrophages, granulocytes, dendritic cells and NK, were selected from the spleen of Y. enterocolitica infected mice and gene expression profiles were analyzed by oligonucleotide microarray. Three groups of C57BL/6 mice were infected intravenous with the Y .enterocolitica pYV+, or the yopP and or the yopH mutants, respectively. It was demonstrated that while the infection with the yopP showed a similar colonization of the spleen to the wild type pYV+ strain, the yopH mutant was highly attenuated. Furthermore, the microarray data revealed a significant difference between the gene expression profiles obtained with yopH strain compared to the wild type pYV+ or with the yopP strain. Intriguingly, the majority of the differentially regulated genes were functionally involved in the immune response, indicating that YopH plays a crucial role in the yersiniosis. Analysis of the transcriptional regulation of this group of genes revealed the presence of a major group of IFN-regulated genes, suggesting that in the early stage of infection the activation via interferon gamma of cells of the innate immunity is essential to overcome the inhibitory effects of YopH. In fact, we could prove that IFN- priming of macrophages can enhance significantly their Yersinia-antimicrobial activity. In order to characterize the molecular mechanisms involved in this process, we performed gene expression analysis of CD11b+ cells isolated from Y. enterocolitica-infected-interferon- receptor deficient mice. The data clearly revealed a panel newly IFN--regulated genes plausibly related to the pathogenesis of Yersinia infection. Further studies will be of interest to characterize the course of yersiniosis in mice in which these genes are disrupted. This study shows that analyses of transcriptional response in host cells directly isolated from in vivo infection can reveal interesting insights into host cell functions and immune responses.

Tipologia di documento:Tesi di dottorato
Parole chiave:Yersinia enterocolitica, Innate immunity, Gene expression
Settori scientifico-disciplinari MIUR:Area 07 Scienze agrarie e veterinarie > VET/05 MALATTIE INFETTIVE DEGLI ANIMALI DOMESTICI
Area 07 Scienze agrarie e veterinarie > VET/02 FISIOLOGIA VETERINARIA
Area 05 Scienze biologiche > BIO/10 BIOCHIMICA
Area 07 Scienze agrarie e veterinarie > VET/06 PARASSITOLOGIA E MALATTIE PARASSITARIE DEGLI ANIMALI
Area 07 Scienze agrarie e veterinarie > VET/01 ANATOMIA DEGLI ANIMALI DOMESTICI
Area 07 Scienze agrarie e veterinarie > VET/03 PATOLOGIA GENERALE E ANATOMIA PATOLOGICA VETERINARIA
Coordinatori della Scuola di dottorato:
Coordinatore del Corso di dottoratoe-mail (se nota)
Paino, Giuseppe
Tutor della Scuola di dottorato:
Tutor del Corso di dottoratoe-mail (se nota)
Fioretti, Alessandro
Stato del full text:Accessibile
Data:2006
Numero di pagine:153
Istituzione:Università degli Studi di Napoli Federico II
Dipartimento o Struttura:Strutture-funzioni e Tecnologie biologiche
Tipo di tesi:Dottorato
Stato dell'Eprint:Inedito
Denominazione del dottorato:Biologia, Patologia e Igiene Ambientale in Medicina Veterinaria
Ciclo di dottorato:XVIII
Numero di sistema:623
Depositato il:30 Luglio 2008
Ultima modifica:04 Febbraio 2009 09:39

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