Responses of microglia in vitro to the gram-positive bacterial component, lipoteichoic acid.
An increase in incidence and severity of gram-positive infections has emerged in the past decade. In this regard, attention has been focused recently on immune responses of microglial cells in the central nervous system to gram-positive bacteria. The underlying immunological and cellular events in microglial activation induced by specific bacterial toxin of gram-positive bacteria, however, have not yet been clarified fully. This study reports that a simple cell wall product, lipoteichoic acid (LTA), derived from gram-positive bacteria (Staphylococcus aureus) could trigger microglial activation in vitro. Microglia challenged with LTA showed intense ruffling of plasma membrane in the form of lamellipodia or rounded up forming cell aggregates. MTT assay and Western blot analysis with anti-proliferating cell nuclear antigen antibody showed a significant microglial proliferation that may be induced at the later phases of LTA treatment with low doses but at the early period with a high dose. Concentrated LTA also caused apoptotic death of cultured microglia showing fragmented nuclei and increased expression of annexin V or caspase 3. In response to LTA, isolated microglia increased the expression of inducible nitric oxide synthase and major histocompatibility complex class II antigen. Microglial LTA receptors such as CD14 molecule, complement receptor type 3, and macrophage scavenger receptor were upregulated concurrently. In conclusion, staphylococcal LTA can exert an immunomodulatory effect on microglial morphology, cell cycle, and immunomolecules, including its receptors.
Jiang-Shieh
Ya-Fen
YF
Department of Anatomy, National Cheng Kung University Medical College, Tainan, Taiwan.
Yeh
Kuei-Ying
KY
Wei
I-Hua
IH
Chang
Chiu-Yun
CY
Chien
Hsiung-Fei
HF
Tsai
Ru-Yin
RY
Chang
Min-Lin
ML
Lee
Ai-Wei
AW
Pai
Man-Hui
MH
Wu
Ching-Hsiang
CH
D000818:Animals; D000831:Animals, Newborn; D017304:Annexin A5 / Q000378:metabolism; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000166:cytology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005455:Fluorescent Antibody Technique / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000737:chemistry*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000276:immunology; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning / Q000379:methods; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009687:Nuclear Proteins / Q000276:immunology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D016601:RNA-Binding Proteins; D051381:Rats; D017208:Rats, Wistar; D013682:Teichoic Acids / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors
D017304:Annexin A5; D000906:Antibodies; D016895:Culture Media, Serum-Free; D000949:Histocompatibility Antigens Class II; D019394:Ki-67 Antigen; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D016601:RNA-Binding Proteins; C484070:Rps15 protein, rat; D013682:Teichoic Acids; D013778:Tetrazolium Salts; D013844:Thiazoles; C009900:lipoteichoic acid; D052247:Nitric Oxide Synthase Type II; C022616:thiazolyl blue