Immunity to mucosal bacteria
Members: Alexander Wenzel (post doc), Maria Magnusson (post doc), Carolyn Nygren (technician), Martina Drábková (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 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.
Another project involves examining how dysfunctional recognition of intestinal flora by immune cells, particularly dendritic cells, contributes to the etiology of inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. This is done using an experimental model where intestinal mucin is lacking. In this way we can study the events that initiate and perpetuate chronic intestinal inflammation. An additional approach to understanding what drives inflammatory bowel diseases involves studying dendritic cell and macrophages from the intestine of patients with Crohn's disease or ulcerative colitis. The aim of these patient studies is to characterize possibly aberrant reactivity of intestinal dendritic cells and macrophages towards bacteria that may contribute to the disease.
Selected publications:
Rydström and Wick, M.J. (2010). Salmonella inhibits monocyte differentiation into CD11chiMHC-IIhicells in a MyD88-dependent fashion. J. Leukoc. Biol. 87:823-832.
Rydström and Wick, M.J. (2009). Monocyte and neutrophil recruitment to intestinal lymphoid tissues during oral Salmonella infection is driven by MyD88-derived chemokines. Eur. J. Immunol. 39:3019-3030.
Sundquist, M. and Wick, M.J. (2009) Salmonella-induced death of CD8α+ dendritic cells but not CD11cintCD11b+ inflammatory cells in vivo via MyD88 and TNFR1. J. Leukoc. Biol. 85:225-234.
Tam, M. and Wick, M.J. (2009). MyD88 and IFN-αβ are differentially required for dendritic cell maturation but dispensable for development of protective memory against Listeria. Immunology 128:429-438.
Tam, M.A.,Sundquist, M., and Wick, M.J. (2008). MyD88 and IFN-αβ differentially control maturation of bystander but not Salmonella-associated dendritic cells or CD11cintCD11b+ cells during infection. Cell. Microbiol. 10:1517-1529.
Tam, M.A., Rydström, A., Sundquist, M. and Wick, M.J. (2008). Early cellular responses to Salmonella infection: dendritic cells, monocytes, and more. Immunol. Rev. 225:140-162.
Rydström, A. and Wick, M.J. (2007). Monocyte recruitment, activation and function in the gut-associated lymphoid tissue during oral Salmonella infection. J. Immunol. 178:5789-5801.
Tam, M.A. and Wick, M.J. (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, M.J. (2005) TNF-dependent and –independent maturation of dendritic cells and recruited CD11cintCD11b+ cells during oral Salmonella infection. J. Immunol. 175:3287-3298.