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Microarray Analysis of Human Monocytes Infected with Francisella tularensis Identifies New Targets of Host Response Subversion

By Jonathan P. Butchar, Thomas J. Cremer, Corey D. Clay, Mikhail A. Gavrilin, Mark D. Wewers, Clay B. Marsh, Larry S. Schlesinger and Susheela Tridandapani

Abstract

Francisella tularensis is a gram-negative facultative bacterium that causes the disease tularemia, even upon exposure to low numbers of bacteria. One critical characteristic of Francisella is its ability to dampen or subvert the host immune response. In order to help understand the mechanisms by which this occurs, we performed Affymetrix microarray analysis on transcripts from blood monocytes infected with the virulent Type A Schu S4 strain. Results showed that expression of several host response genes were reduced such as those associated with interferon signaling, Toll-like receptor signaling, autophagy and phagocytosis. When compared to microarrays from monocytes infected with the less virulent F. tularensis subsp. novicida, we found qualitative differences and also a general pattern of quantitatively reduced pro-inflammatory signaling pathway genes in the Schu S4 strain. Notably, the PI3K / Akt1 pathway appeared specifically down-regulated following Schu S4 infection and a concomitantly lower cytokine response was observed. This study identifies several new factors potentially important in host cell subversion by the virulent Type A F. tularensis that may serve as novel targets for drug discovery

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:2488368
Provided by: PubMed Central
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    1. (2007). Francisella tularensis replicates within alveolar type II epithelial cells in vitro and in vivo following inhalation.
    2. (1983). Phagocytosis and killing of Francisella tularensis by human polymorphonuclear leukocytes.
    3. (1975). Phagocytosis of Francisella tularensis by Rhesus monkey peripheral leukocytes.
    4. (1986). Some diagnostic, biologic and morphologic characteristics of Francisella
    5. (2007). The role of the activated macrophage in clearing Listeria monocytogenes infection.
    6. (2004). Virulent and avirulent strains of Francisella tularensis prevent acidification and maturation of their phagosomes and escape into the cytoplasm in human macrophages.

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