Pathogen-Specific Innate Immune Response
This chapter summarizes our studies on the three toll-like receptor pathways, namely TLR4, TLR2, and TLR3, induced by lipopolysaccharides (LPS), peptidoglycan (PGN), and double-stranded RNA (dsRNA) in antigen presenting cells (APC). The particular emphasis is on the activation of human innate immune responses via cytokine and chemokine production. Three different measurements have been performed on monocytic and dendritic cells as model APCs: (i) the expression of various cytokine and chemokine genes by real-time PCR, (ii) the release of the cytokines and chemokines by ELISA, and (iii) gene expression analysis by cytokine and chemokine pathway-specific and whole genome microarrays. Real-time PCR and ELISA enable us to identify cytokines and chemokines that are produced specifically upon LPS, PGN, or dsRNA stimulation. Subsequently, microarray studies and appropriate validation experiments help us to identify genes involved in the upstream pathways that cause the induction of cytokines and chemokines. It is evident that TLR4-LPS, TLR2-PGN, and TLR3-dsRNA pathways are distinguished by the specific set of cytokines and chemokines they induce as well as by the upstream signaling events.
KeywordsInnate Immune Response Chemokine Gene Single Arrow Model APCs Chemokine Protein
Unable to display preview. Download preview PDF.
- Baumgartner, B., Weber, M., Quirling, M., Fischer, C., Page, S., Adam, M., Von Schilling, C., Waterhouse, C., Schmid, C., Neumeier, D., and Brand, K. (2002) Increased IkappaB kinase activity is associated with activated NF-kappaB in acute myeloid blasts. Leukemia 16(10):2062-2071.PubMedCrossRefGoogle Scholar
- de Bouteiller, O., Merck, E., Hasan, U.A., Hubac, S., Benguigui, B., Trinchieri, G., Bates, E.E., and Caux, C. (2005) Recognition of double-stranded RNA by human toll-like receptor 3 and downstream receptor signaling requires multimerization and an acidic pH. J Biol Chem 280(46):38133-38145.PubMedCrossRefGoogle Scholar
- Hacker, H. and Karin, M. (2006) Regulation and function of IKK and IKK-related kinases. Sci STKE 2006(357):re13.Google Scholar
- Hoebe, K., Janssen, E.M., Kim, S.O., Alexopoulou, L., Flavell, R.A., Han, J., and Beutler, B. (2003) Upregulation of costimulatory molecules induced by lipopolysaccharide and double-stranded RNA occurs by Trif-dependent and Trif-independent pathways. Nat Immunol 4(12):1223-1229.PubMedCrossRefGoogle Scholar
- Weiss-Haljiti, C., Pasquali, C., Ji, H., Gillieron, C., Chabert, C., Curchod, M.L., Hirsch, E., Ridley, A.J., van Huijsduijnen, R.H., Camps, M., and Rommel, C. (2004) Involvement of phosphoinositide 3-kinase gamma, Rac, and PAK signaling in chemokine-induced macrophage migration. J Biol Chem 279(41):43273-43284.PubMedCrossRefGoogle Scholar
- Zeytun, A., van Velkinburgh, J.C., and Gupta, G. Unpublished Data.Google Scholar