Microglial Activation by <i>Citrobacter koseri</i> Is Mediated by TLR4- and MyD88-Dependent Pathways

Liu, Shuliang; Kielian, Tammy

doi:10.4049/jimmunol.0900083

Cited by 32 publications

(25 citation statements)

References 66 publications

(75 reference statements)

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“…C. koseri induced proinflammatory mediator release was significantly reduced in TLR4 mutant and MyD88 KO microglia compared with wild-type cells, indicating that both TLR4 and MyD88 were essential for the immune response of microglial cells to C. koseri [56].…”

Section: Other Bacterial Infectionmentioning

confidence: 99%

Toll-like receptors in inflammation of the central nervous system

Kong

2011

International Immunopharmacology

114

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Section: Other Bacterial Infectionmentioning

confidence: 99%

Toll-like receptors in inflammation of the central nervous system

Kong

2011

International Immunopharmacology

114

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“…The mechanisms that trigger retinal microglial activation in bacterial endophthalmitis are generally unknown. However, based on bacterial meningitis (18,36) and brain abscess (24) studies, it can be postulated that Toll-like receptors (TLRs) are likely to…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 2 Ligand Pretreatment Attenuates Retinal Microglial Inflammatory Response but Enhances Phagocytic Activity toward Staphylococcus aureus

et al. 2012

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ABSTRACTStaphylococcus aureusis a leading cause of severe endophthalmitis, which often results in vision loss in some patients. Previously, we showed that Toll-like receptor 2 (TLR2) ligand pretreatment prevented the development of staphylococcal endophthalmitis in mice and suggested that microglia might be involved in this protective effect (Kumar A, Singh CN, Glybina IV, Mahmoud TH, Yu FS. J. Infect. Dis. 201:255–263, 2010). The aim of the present study was to understand how microglial innate response is modulated by TLR2 ligand pretreatment. Here, we demonstrate thatS. aureusinfection increased the CD11b+CD45+microglial/macrophage population in the C57BL/6 mouse retina. Using cultured primary retinal microglia and a murine microglial cell line (BV-2), we found that these cells express TLR2 and that its expression is increased upon stimulation with bacteria or an exclusive TLR2 ligand, Pam3Cys. Furthermore, challenge of primary retinal microglia withS. aureusand its cell wall components peptidoglycan (PGN) and lipoteichoic acid (LTA) induced the secretion of proinflammatory mediators (tumor necrosis factor alpha [TNF-α] and MIP-2). This innate response was attenuated by a function-blocking anti-TLR2 antibody or by small interfering RNA (siRNA) knockdown of TLR2. In order to assess the modulation of the innate response, microglia were pretreated with a low dose (0.1 or 1 μg/ml) of Pam3Cys and then challenged with liveS. aureus. Our data showed thatS. aureus-induced production of proinflammatory mediators is dramatically reduced in pretreated microglia. Importantly, microglia pretreated with the TLR2 agonist phagocytosed significantly more bacteria than unstimulated cells. Together, our data suggest that TLR2 plays an important role in retinal microglial innate response toS. aureus, and its sensitization inhibits inflammatory response while enhancing phagocytic activity.

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“…Specifically, proinflammatory mediator release was significantly reduced in both TLR4 mutant and MyD88 KO primary microglia following C. koseri exposure [108]. In contrast, MyD88, but not TLR4, proved critical for CNS C. koseri infection in vivo .…”

Section: Roles For Tlrs During Cns Infectionmentioning

confidence: 99%

Toll-like receptors in health and disease in the brain: mechanisms and therapeutic potential

2011

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The discovery of mammalian Toll-like receptors (TLRs), first identified in 1997 based on their homology with Drosophila Toll, greatly altered our understanding of how the innate immune system recognizes and responds to diverse microbial pathogens. TLRs are evolutionarily conserved type I transmembrane proteins expressed in both immune and non-immune cells and are typified by N-terminal leucine-rich repeats and a highly conserved C-terminal domain termed the Toll/interleukin (IL)-1 receptor (TIR) domain. Upon stimulation with their cognate ligands, TLR signaling elicits the production of cytokines, enzymes, and other inflammatory mediators that can impact several aspects of central nervous system (CNS) homeostasis and pathology. For example, TLR signaling plays a crucial role in initiating host defense responses during CNS microbial infection. Furthermore, TLRs are targets for many adjuvants which help shape pathogen-specific adaptive immune responses in addition to triggering innate immunity. Our knowledge of TLR expression and function in the CNS has greatly expanded over the last decade, with new data revealing that TLRs also impact non-infectious CNS diseases/injury. In particular, TLRs recognize a number of endogenous molecules liberated from damaged tissues and, as such, influence inflammatory responses during tissue injury and autoimmunity. Also, recent studies have implicated TLR involvement during neurogenesis and learning and memory in the absence of any underlying infectious etiology. Due to their presence and immune regulatory role within the brain, TLRs represent an attractive therapeutic target for numerous CNS disorders and infectious diseases. However, it is clear that TLRs can exert either beneficial or detrimental effects in the CNS, which likely depend on the context of tissue homeostasis or pathology. Therefore, any potential therapeutic manipulation of TLRs will require an understanding of the signals governing specific CNS disorders to achieve tailored therapy.

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Microglial Activation by Citrobacter koseri Is Mediated by TLR4- and MyD88-Dependent Pathways

Cited by 32 publications

References 66 publications

Toll-like receptors in inflammation of the central nervous system

Toll-like receptors in inflammation of the central nervous system

Toll-Like Receptor 2 Ligand Pretreatment Attenuates Retinal Microglial Inflammatory Response but Enhances Phagocytic Activity toward Staphylococcus aureus

Toll-like receptors in health and disease in the brain: mechanisms and therapeutic potential

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