Neuroimmune interactions are most critical to protect the nervous system from dangerous pathogens but also have a major impact on regenerative processes in all parts of the neuromuscular system. However, the immune reaction is a two edged sword as an excessive host immune response can cause more harm than good. Some of the most frequent neurological diseases are caused by autoimmune mechanisms in which the immune system attacks the nervous systems without the presence of pathogens. The mechanistic understanding of both the good and the ugly neuroimmune responses during health and disease is the necessary foundation for future therapeutic strategies.
Our research group focuses on the role of macrophages in neuroimmunological diseases. Macrophages can actively modulate the inflammatory milieu by secreting pro- and anti-inflammatory cytokines. They are a key effector cell population of the immune system. In many circumstances, the state of macrophage activation determines the outcome of an immune-mediated disease. Ongoing research projects are characterizing macrophage populations in models of Multiple Sclerosis (MS), the Guillain-Barré sydrome (GBS) or Herpes encephalitis. .
The second interest of the group is the role and function of chemokines in neuroinflammation. Chemokines are important messenger molecules. They orchestrate the distribution of immune cells inside the nervous system and therefore are a very attractive therapeutic target. Current projects focus on the role of the CXCR3 chemokine system, which has a major impact on activated T cells and macrophages. Transgenic mice with a CNS specific expression of the CXCR3 ligands CXCL9 and CXCL10 are used to reveal their specific role in neuroinflammatory diseases.
Carter SL, Müller M, Manders PM, Campbell IL. Induction of the genes for Cxcl9 and Cxcl10 is dependent on IFN-gamma but shows differential cellular expression in experimental autoimmune encephalomyelitis and by astrocytes and microglia in vitro. Glia 2007; 55:1728-1739.
Müller M, Berghoff M, Kobsar I, Kiefer R, Martini R. Macrophage colony stimulating factor is a crucial factor for the intrinsic macrophage response in mice heterozygously deficient for the myelin protein P0. Exp Neurol 2007; 203:55-62.
Müller M, Carter SL, Hofer MJ, Manders P, Getts DR, Getts MT, Dreykluft A, Lu B, Gerard C, King NJ and others. CXCR3 signaling reduces the severity of experimental autoimmune encephalomyelitis by controlling the parenchymal distribution of effector and eegulatory T cells in the central nervous system. J Immunol 2007; 179:2774-2786.
Miu J, Mitchell AJ, Müller M, Carter SL, Manders PM, McQuillan JA, Saunders BM, Ball HJ, Lu B, Campbell IL. Chemokine gene expression during fatal murine cerebral malaria and protection due to CXCR3 deficiency. J Immunol 2008; 180:1217-30.
Müller M, Wacker K, Getts D, Ringelstein EB, Kiefer R. Further evidence for a crucial role of resident endoneurial macrophages in peripheral nerve disorders: Lessons from acrylamide-induced neuropathy. Glia 2008; 56:1005-1016.
Getts DR, Terry RL, Getts MT, Müller M, Rana S, Shrestha B, Radford J, Van Rooijen N, Campbell IL, King NJ. Ly6c+ "inflammatory monocytes" are microglial precursors recruited in a pathogenic manner in West Nile virus encephalitis. J Exp Med. 2008, 205(10): 2319-37
Quintana A*, Müller M*, Frausto RF, Ramos R, Getts DR, Sanz E, Hofer MJ, Krauthausen M, King NJC, Hidalgo J, Campbell IL. Site-specific production of IL-6 in the central nervous system retargets and enhances the inflammatory response in experimental autoimmune encephalomyelitis. J Immunol 2009, 183(3):2079-88. (*equal contribution)