“Eat me” and “don't eat me” signals govern the innate immune response and tissue repair in the CNS: emphasis on the critical role of the complement system

Elward, Kristina; Gasque, Philippe

doi:10.1016/s0161-5890(03)00109-3

Cited by 187 publications

(153 citation statements)

References 80 publications

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“…They are a heterogenous population of resident macrophages that monitor the local environment by interacting with neurons, glia, and endothelium and that react to stresses, including infection, trauma, and retinal detachment, by release of proinflammatory cytokines (11) and clearance of necrotic or apoptotic cells via phagocytosis (12). Microglial cells become activated and help to resolve local injury (13,14), but unrelenting stresses cause persistent inflammatory responses.…”

Section: Topographic and Cellular Organization Of The Retinamentioning

confidence: 99%

“…Activated microglia produce chemokines such as monocyte chemoattractant protein-1 (11), inducing expression of adhesion molecules, which can promote the leukostasis of neutrophils, on endothelium (65) and potentially inducing the extravasation of inflammatory macrophages (66). In addition, elevated levels of complement and reduced levels of complement inhibitors (67) and acute-phase proteins (68) are likely key events in the phagocytic clearance of necrotic and apoptotic neurons (12). Recent evidence strongly suggests that inflammation involving vessels and neural tissue occurs early in experimental (11,64,65,67,69) and human (70) retinopathy, involving humoral and cellular components of innate immunity.…”

Section: Fig 2 Functional Anatomy Of the Retina Metabolic Interactmentioning

confidence: 99%

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Diabetic Retinopathy

et al. 2006

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Diabetic retinopathy remains a frightening prospect to patients and frustrates physicians. Destruction of damaged retina by photocoagulation remains the primary treatment nearly 50 years after its introduction. The diabetes pandemic requires new approaches to understand the pathophysiology and improve the detection, prevention, and treatment of retinopathy. This perspective considers how the unique anatomy and physiology of the retina may predispose it to the metabolic stresses of diabetes. The roles of neural retinal alterations and impaired retinal insulin action in the pathogenesis of early retinopathy and the mechanisms of vision loss are emphasized. Potential means to overcome limitations of current animal models and diagnostic testing are also presented with the goal of accelerating therapies to manage retinopathy in the face of ongoing diabetes. Diabetes 55:2401-2411, 2006 D espite years of clinical and laboratory investigation, diabetic retinopathy remains the leading cause of vision impairment and blindness among working-age adults, yet the fundamental cause(s) remains uncertain. Retinal photocoagulation to reduce neovascularization and macular edema was developed in the 1950s and is still the standard of care (1). The number of people worldwide at risk of developing vision loss from diabetes is predicted to double over the next 30 years (2), so it is imperative to develop better means to identify, prevent, and treat retinopathy in its earliest stages rather than wait for the onset of vision-threatening lesions. Progress in these areas requires a new perspective on the problem that includes the roles of the neural retina, impaired insulin action, and inflammation. In this way, established neurobiological principles can inform us how diabetes impairs vision, and knowledge of metabolism, inflammation, and regenerative medicine may lead to new treatments.This perspective will discuss how the unique anatomy and physiology of the retina may render it vulnerable to the metabolic derangements of diabetes and lead to impaired vision. The intent of this unconventional approach is to encourage consideration of new opportunities for investigations that will advance the field. NORMAL RETINAL STRUCTURE AND PHYSIOLOGY Topographic and cellular organization of the retina.It is instructive to consider the functional organization of the retina (literally a network) to better understand the impact of diabetes (http://webvision.med.utah.edu). The retina is a transparent layer of neural tissue between the retinal pigmented epithelium and the vitreous body. Normal vision depends on intact cell-cell communication among the neuronal, glial, microglial, vascular, and pigmented epithelial cells of the retina. The fundamental functions of the retina are to capture photons, convert the photochemical energy into electrical energy, integrate the resulting action potentials, and transmit them to the occipital lobe of the brain, where they are deciphered and interpreted into recognizable images. The retina is partitioned from the syst...

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Section: Topographic and Cellular Organization Of The Retinamentioning

confidence: 99%

Section: Fig 2 Functional Anatomy Of the Retina Metabolic Interactmentioning

confidence: 99%

Diabetic Retinopathy

et al. 2006

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“…While acquired immune responses operate later in an infection and are highly specific for the pathogen that induces them, the innate immune responses react immediately after exposure to pathogens and serve as the first line of host defense. The innate immune system depends on the pattern recognizing receptors (PRRs), e.g., components of the complement system and the Toll-like receptor family, that detect the pathogen-associated molecular patterns (PAMPs) and execute subsequent immune cell responses [16][17][18] (Fig. 2A).…”

Section: The Toll-like Receptor Familymentioning

confidence: 99%

“…The expression of these receptors in immune cells is linked unequivocally to the detection of self from non-self [18]. However, an increasing number of reports indicate that TLRs are expressed and functional in non-immune, somatic cells such as adipose cells [22], mouse bone marrow derived mesenchymal stem cells (MSCs) [20] and human adipose tissue and bone marrow derived MSCs [23].…”

Section: Expression Of Tlrs In Non-immune Cellsmentioning

confidence: 99%

The involvement of the Toll-like receptor family in ovulation

Liu

Shimada

Richards

2008

J Assist Reprod Genet

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Introduction Ovulation is similar to an inflammatory response and is associated with increased production of prostaglandins as well as local growth regulatory factors. However, the expression and function of innate immune cell-related genes in non-immune cells within the ovary has been reported recently and provides a novel and important regulatory system during ovulation. Discussion Several members of the Toll-like receptor (TLR) surveillance system are expressed in granulosa cells and cumulus cells. These receptors can be activated by pathogens as well as endogenous ligands leading to the induction and release of potent cytokines and chemokines from cumulus cells. Conclusion These inflammatory factors exert potent effects on cumulus cell-oocyte expansion, ovulation, transport and fertilization indicating that ovulation is a more complex immune-inflammatory process than previously recognized.

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“…Beside its crucial role in the killing of invading microorganisms, C proteins or protein fragments that are generated during complement activation are potential regulators of the host immune response (12,23). In pneumococcal meningitis, the inflammatory host response has been indicated to cause damage to the brain, thus accounting for the outcome of meningitis (for review, Refs.…”

mentioning

confidence: 99%

Complement C1q and C3 Are Critical for the Innate Immune Response to Streptococcus pneumoniae in the Central Nervous System

Rupprecht

Angele

Klein

et al. 2007

The Journal of Immunology

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Previous studies suggest that the complement system can contribute to limiting pneumococcal outgrowth within the CNS. In this study, we evaluated the role of the complement system in the activation of the innate immune response and the development of the prognosis-relevant intracranial complications in a murine model of pneumococcal meningitis. Thereby, we used mice deficient in C1q, lacking only the classical pathway, and C3, lacking all three complement activation pathways. At 24 h after intracisternal infection, bacterial titers in the CNS were almost 12- and 20-fold higher in C1q- and C3-deficient-mice, respectively, than in wild-type mice. Mean CSF leukocyte counts were reduced by 47 and 73% in C1q- and C3-deficient-mice, respectively. Intrathecal reconstitution with wild-type serum in C3-deficient mice restored both the ability of mice to combat pneumococcal infection of the CSF and the ability of leukocytes to egress into the CSF. The altered recruitment of leukocytes into the CSF of C3-deficient mice was paralleled by a strong reduction of the brain expression of cytokines and chemokines. The dampened immune response in C3-deficient mice was accompanied by a reduction of meningitis-induced intracranial complications, but, surprisingly, also with a worsening of short-term outcome. The latter seems to be due to more severe bacteremia (12- and 120-fold higher in C1q- and C3-deficient-mice, respectively) and, consecutively, more severe systemic complications. Thus, our study demonstrated for the first time that the complement system plays an integral role in mounting the intense host immune response to Streptococcus pneumoniae infection of the CNS.

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“Eat me” and “don't eat me” signals govern the innate immune response and tissue repair in the CNS: emphasis on the critical role of the complement system

Cited by 187 publications

References 80 publications

Diabetic Retinopathy

Diabetic Retinopathy

The involvement of the Toll-like receptor family in ovulation

Complement C1q and C3 Are Critical for the Innate Immune Response to Streptococcus pneumoniae in the Central Nervous System

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