title: Microglial activation and expression of immune-related genes in a rat ex vivo nervous system model after infection with Listeria monocytogenes.
abstract: A wide variety of microorganisms has previously been identified as causes of brain infection. Among them, Listeria monocytogenes has a particular tropism for the central nervous system. To gain knowledge about the immune response elicited by L. monocytogenes in the brain, we used a rat ex vivo organotypic nervous system culture as a model for Listeria infection. Scanning electron microscopy (SEM) revealed that activated microglial cells showing a typical amoeboid morphology are quickly recruited to the surface of the explants after the infection. After bacterial engulfment, these cells appear to act as Trojan horses, releasing the engulfed bacteria inside the brain tissue. We describe cycles of microglial phagocytosis, necrotic cell death and the subsequent removal of cell debris for the first time. Furthermore, we used this ex vivo model to assess the expression profiles of immune relevant genes up to 24 h postinfection by means of q-PCR-arrays, finding that a number of inflammation-promoting genes are upregulated. Shortly after infection by L. monocytogenes, upregulated genes were those that encoded molecules involved in Th1 responses, being the Ccl2 chemokine and members of the interleukin1-β family the most abundant immunomodulatory signals expressed. After 5 h of infection, L. monocytogenes caused a substantial increase in the expression of TLR1 and TLR2 genes, as well as in several downstream genes of the TLR signaling pathways.
authors: Servicio de Microbiología, Hospital Universitario Marqués de Valdecilla-IFIMAV, Santander, Cantabria, Spain.
authors: Sara
authors: S
authors: Remuzgo-Martínez
authors: Lilian
authors: L
authors: Pilares-Ortega
authors: Jose M
authors: JM
authors: Icardo
authors: Elsa Maria
authors: EM
authors: Valdizán
authors: Verónica Inés
authors: VI
authors: Vargas
authors: Angel
authors: A
authors: Pazos
authors: Jose
authors: J
authors: Ramos-Vivas
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001927:Brain Diseases / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008089:Listeria monocytogenes / Q000235:genetics* / Q000254:growth & development / Q000276:immunology; D008088:Listeriosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D017628:Microglia / Q000382:microbiology* / Q000473:pathology* / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6