Both TLR2 and TLR4 are required for the effective immune response in Staphylococcus aureus-induced experimental murine brain abscess.
Toll-like receptors (TLRs) play central roles in the innate reaction to bacterial products and transmit specific immune responses against these pathogens. TLRs are expressed on numerous cell types, including innate immune cells, and on astrocytes, neurons, and microglial cells of the central nervous system (CNS). Lipoproteins and lipopolysaccharides are specifically recognized by TLR2 and TLR4, respectively. We examined the in vivo role of TLR2 and TLR4 in Staphylococcus aureus-induced brain abscess. Phenotypically, 87% of TLR2(-/-) mice and 43% of TLR4(-/-) mice died whereas all wild-type (WT) mice recovered. Clearance of bacteria from the CNS was significantly delayed in TLR2(-/-) mice compared with TLR4(-/-) and WT animals. Recruitment of granulocytes and macrophages to the CNS, as well as microglial activation and expansion, was up-regulated in TLR2(-/-) mice. Although inflammation persisted especially in the CNS of TLR2(-/-) mice, but also of TLR4(-/-) mice, WT mice terminated the infection more effectively. Collectively, these data show that the immune response to experimental S. aureus-induced brain abscess depends crucially on the recognition of S. aureus by TLR2 but that TLR4 is also required for an optimal intracerebral immune response in this disorder.
Stenzel
Werner
W
Department of Neuropathology, University of Cologne, Joseph-Stelzmann-Strasse 9, D-50931 Köln, Germany. w.stenzel@uni-koeln.de
Soltek
Sabine
S
Sanchez-Ruiz
Monica
M
Akira
Shizuo
S
Miletic
Hrvoje
H
Schlüter
Dirk
D
Deckert
Martina
M
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D005434:Flow Cytometry; D006098:Granulocytes / Q000378:metabolism; D006720:Homozygote; D007107:Immune System; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D013211:Staphylococcus aureus / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation
C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4