title: Toll-like receptor 2 modulates the proinflammatory milieu in Staphylococcus aureus-induced brain abscess.
abstract: Toll-like receptor 2 (TLR2) is a pattern recognition receptor (PRR) that plays an important role in innate immune recognition of conserved structural motifs on a wide array of pathogens, including Staphylococcus aureus. To ascertain the functional significance of TLR2 in the context of central nervous system (CNS) parenchymal infection, we evaluated the pathogenesis of S. aureus-induced experimental brain abscess in TLR2 knockout (KO) and wild-type (WT) mice. The expression of several proinflammatory mediators, including inducible nitric oxide synthase, tumor necrosis factor alpha, and macrophage inflammatory protein-2, was significantly attenuated in brain abscesses of TLR2 KO mice compared to WT mice during the acute phase of infection. Conversely, interleukin-17 (IL-17), a cytokine produced by activated and memory T cells, was significantly elevated in lesions of TLR2 KO mice, suggesting an association between innate and adaptive immunity in brain abscess. Despite these differences, brain abscess severity in TLR2 KO and WT animals was similar, with comparable mortality rates, bacterial titers, and blood-brain barrier permeability, implying a role for alternative PRRs. Expression of the phagocytic PRRs macrophage scavenger receptor type AI/AII and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) was increased in brain abscesses of both TLR2 KO and WT mice compared to uninfected animals. However, LOX-1 induction in brain abscesses of TLR2 KO mice was significantly attenuated compared to WT animals, revealing that the TLR2-dependent signal(s) influence LOX-1 expression. Collectively, these findings reveal the complex nature of gram-positive bacterial recognition in the CNS which occurs, in part, through engagement of TLR2 and highlight the importance of receptor redundancy for S. aureus detection in the CNS.
authors.affiliation: Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, 4301 W. Markham St., Slot 846, Little Rock, AR 72205, USA. KielianTammyL@uams.edu
authors.forename: Tammy
authors.initials: T
authors.lastname: Kielian
authors.forename: Anessa
authors.initials: A
authors.lastname: Haney
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Mayes
authors.forename: Sarita
authors.initials: S
authors.lastname: Garg
authors.forename: Nilufer
authors.initials: N
authors.lastname: Esen
mesh_terms: D000818:Animals; D001922:Brain Abscess / Q000150:complications / Q000276:immunology / Q000382:microbiology* / Q000473:pathology*; D054426:Chemokine CXCL2; D018925:Chemokines / Q000096:biosynthesis; D005786:Gene Expression Regulation; D007249:Inflammation / Q000150:complications / Q000473:pathology; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction; D013203:Staphylococcal Infections / Q000150:complications / Q000276:immunology / Q000473:pathology*; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D018836:Inflammation Mediators; D020381:Interleukin-17; D018950:Lipopolysaccharide Receptors; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha