Immunity to intracellular Salmonella

During intestinal or systemic pathogenesis, Salmonella is confronted with various immune defense mechanisms of the host. These defenses involve innate immune functions such as phagocytosis, exposure to reactive oxygen and nitrogen intermediates (ROI and RNI, respectively) or antimicrobial peptides, as well as adaptive immune functions such as production of specific antibodies and cytotoxic T-cells. We have previously demonstrated that intracellular Salmonella is protected against RNI by means of the SPI2-T3SS-mediated modification of host cell functions. Intracellular Salmonella are also able to interfere with the induction of an adaptive immune response by interfering with antigen-presentation and stimulation of T-cell responses by infected dendritic cells. We determined the role the SPI2-T3SS in this manipulation and identified a subset of SPI2-T3SS effector proteins involved in this phenotype.
We recently investigated the role of the complex lipopolysaccharide (LPS) of Salmonella enterica during pathogenesis and observed that the O-antigen of the LPS contributes to the manipulation of host cell functions and delays the recognition of the pathogen by the host immune system.

Future directions are to

• understand how intracellular Salmonella interferes with cell functions of dendritic cells
• analyze the role of LPS O-antigen in the intracellular fate of Salmonella

Collaborations

• Dr. Jonathan Jantsch, Universitätsklinikum Erlangen
• Prof. Dr. Mathias Hornef, Medizinische Hochschule Hannover

Original papers

Duerr, C.U., Zenk, S.F., Chassin, C., Pott, J., Gutle, D., Hensel, M., and Hornef, M.W. (2009). O-antigen delays lipopolysaccharide recognition and impairs antibacterial host defense in murine intestinal epithelial cells. PLoS Pathogens 5, e1000567.
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Zenk, S.F., Jantsch, J., and Hensel, M. (2009). Role of Salmonella enterica lipopolysaccharide in activation of dendritic cell functions and bacterial containment. J Immunol 183, 2697-2707.
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Halici, S., Zenk, S.F., Jantsch, J., and Hensel, M. (2008). Functional analysis of the Salmonella Pathogenicity Island 2-mediated inhibition of antigen presentation in dendritic cells. Infect Immun 76, 4924-4933.
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Jantsch, J., Turza, N., Volke, M., Eckardt, K.U., Hensel, M., Steinkasserer, A., Willam, C., and Prechtel, A.T. (2008). Small interfering RNA (siRNA) delivery into murine bone marrow-derived dendritic cells by electroporation. J Immunol Methods 337, 71-77.
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Jantsch, J., Chakravortty, D., Turza, N., Prechtel, A.T., Buchholz, B., Gerlach, R.G., Volke, M., Glasner, J., Warnecke, C., Wiesener, M.S., et al. (2008). Hypoxia and Hypoxia-Inducible Factor-1{alpha} modulate lipopolysaccharide-induced dendritic cell activation and function. J Immunol 180, 4697-4705.
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Eswarappa, S.M., Panguluri, K.K., Hensel, M., and Chakravortty, D. (2008). The yejABEF operon of Salmonella confers resistance to antimicrobial peptides and contributes to its virulence. Microbiology 154, 666-678.
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