Group leader: This e-mail address is being protected from spambots. You need JavaScript enabled to view it (Professor, Ph.D.)
Members: Malin Sundquist (Ph.D. student), Miguel Tam (Ph.D. student), Anna Rydström (Ph.D. student).

The innate immune system provides the first line of defense against infection. An innate immune response is started  when toll-like receptors (TLRs), which are expressed by many cells of the immune system including macrophages and dendritic cells, bind conserved bacterial components like lipopolysaccharide or flagella. This triggers signaling cascades that result production of cytokines important in controlling the infection. It also initiates production of chemokines that recruit various cell types to the infected tissue. In addition, TLR signaling induces dendritic cell maturation, a process that transforms them into cells uniquely capable of activating naïve T cells to start a specific immune response. Thus, TLR signaling triggers innate immunity and induces long term, specific immunity to the infection.

The aim of this project is to understand the TLR signaling pathways involved in generating immunity to the food-borne pathogens Salmonella and Listeria. These bacteria are acquired orally, and cells in the lymphoid organs draining the intestine are the first to respond to the infection. Both Salmonella and Listeria are intracellular bacteria, but due to distinct features such as cell wall composition and location in infected cells, trigger a partially overlapping set of TLRs.

The group focuses on the response of dendritic cells and monocytes/macrophages to oral infection with Salmonella and Listeria. We aim to decipher the TLR signaling pathways involved in inducing dendritic cell maturation and T cell function during infection with these bacteria. The role of distinct dendritic cell subsets, as well as the mechanisms driving recruitment and activation of dendritic cells and monocytes during infection, is also studied. The project allows us to understand both the bacterial and host factors required to recruit and activate the cells that initiate immunity to these intracellular pathogens.

Important publications:
Tam MA and Wick MJ. (2006)  Differential expansion, activation and effector functions of conventional and plasmacytoid dendritic cells in mouse tissues transiently infected with Listeria monocytogenes.  Cell. Microbiol. 8:1172-1187.

Sundquist M and Wick MJ. (2005) TNF-α-dependent and –independent maturation of dendritic cells and recruited CD11c^intCD11b⁺ cells during oral Salmonella infection. J. Immunol. 175:3287-3298.

Johansson C and Wick MJ. (2004) Liver dendritic cells present bacterial antigens and produce cytokines upon Salmonella encounter.  J. Immunol. 172:2496-2503.

Wick MJ. (2004) Living in the danger zone: Innate immunity to intracellular bacteria. Curr. Opin. Microbiol. 7:51-57.

Sundquist M, Rydström A and Wick MJ. (2004) Immunity to Salmonella from a dendritic point of view.  Cell. Microbiol. 6:1-11.