TLR3 Deficiency in Patients with Herpes Simplex Encephalitis

Zhang, Shen-Ying; Jouanguy, Emmanuelle; Ugolini, Sophie; Smahi, Asma; Elain, Gaelle; Romero, Pedro; Segal, David M.; Sancho‐Shimizu, Vanessa; Lorenzo, Lazaro; Puel, Anne; Pïcard, Capucine; Chapgier, Ariane; Plancoulaine, Sabine; Titeux, Matthias; Cognet, Céline; Bernuth, Horst von; Ku, Cheng-Lung; Casrouge, Armanda; Zhang, Xin Xin; Barreiro, Luis B.; Leonard, Joshua N.; Hamilton, Claire; Lebon, Pierre; Héron, Bénédicte; Vallée, Louis; Quintana-Murci, Lluı́s; Hovnanian, Alain; Rozenberg, Flore; Vivier, Éric; Geissmann, Frédéric; Tardieu, Marc; Abel, Laurent; Casanova, Jean‐Laurent

doi:10.1126/science.1139522

Cited by 1,000 publications

(1,026 citation statements)

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“…However one study has reported that TLR3 is important in the human response 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 29 to HSV induced encephalitis (HSE). In this study it was found that two children with a heterozygous mutation in TLR3 were specifically predisposed to HSE [98].…”

Section: Tlrs and Herpes Simplex Encephalitismentioning

confidence: 67%

Evaluating the role of Toll-like receptors in diseases of the central nervous system

Carty

Bowie

2011

Biochemical Pharmacology

134

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A key part of the innate immune system is a network of pattern recognition receptors (PRRs) and their associated intracellular signalling pathways. Toll-like receptors (TLRs) are one such group of PRRs that detect pathogen associated molecular patterns (PAMPs). Activation of the TLRs with their respective agonists results in the activation of intracellular signalling pathways leading to the expression of proinflammatory mediators and anti-microbial effector molecules. Activation of the innate immune system through TLRs also triggers the adaptive immune response, resulting in a comprehensive immune program to eradicate invading pathogens. It is now known that immune surveillance and inflammatory responses occur in the central nervous system (CNS). Furthermore it is becoming increasingly clear that TLRs have a role in such CNS responses andare also implicated in the pathogenesis of a number of conditions in the CNS, such as Alzheimer's, stroke and multiple sclerosis. This is likely due to the generation of endogenous TLR agonists in these conditions which amplifies a detrimental neurotoxic inflammatory response. However TLRs in some situations can be neuroprotective, if triggered in a favourable context. This review aims to examine the recent literature on TLRs in the CNS thus demonstrating their importance in a range of infectious and non-infectious diseases of the brain.

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Section: Tlrs and Herpes Simplex Encephalitismentioning

confidence: 67%

Evaluating the role of Toll-like receptors in diseases of the central nervous system

Carty

Bowie

2011

Biochemical Pharmacology

134

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“…IFNs contribute to host resistance to viral proliferation through activation of the Jak-Stat signaling pathway [27], and by triggering production of both RNAse enzymes that destroy cellular RNA (both host and viral) and double-stranded RNA-dependent protein kinase, which halts cellular translation [28]. Deficiencies in the immune response to HSV (e.g., defects in the TLR-3 pathway, including TLR3 itself, UNC93B1, TIR-domain-containing adapter-inducing IFN-β, tumor necrosis factor receptorassociated factor-3, TANK-binding kinase 1, or IFN regulatory factor-3) leave the host susceptible to HSVE [29][30][31].…”

Section: Introductionmentioning

confidence: 99%

Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management

2016

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Herpetic infections have plagued humanity for thousands of years, but only recently have advances in antiviral medications and supportive treatments equipped physicians to combat the most severe manifestations of disease. Prompt recognition and treatment can be lifesaving in the care of patients with herpes simplex-1 virus encephalitis, the most commonly identified cause of sporadic encephalitis worldwide. Clinicians should be able to recognize the clinical signs and symptoms of the infection and familiarize themselves with a rational diagnostic approach and therapeutic modalities, as early recognition and treatment are key to improving outcomes. Clinicians should also be vigilant for the development of acute complications, including cerebral edema and status epilepticus, as well as chronic complications, including the development of autoimmune encephalitis associated with antibodies to the N-methyl-D-aspartate receptor and other neuronal cell surface and synaptic epitopes. Herein, we review the pathophysiology, differential diagnosis, and clinical and radiological features of herpes simplex virus-1 encephalitis in adults, including a discussion of the most common complications and their treatment. While great progress has been made in the treatment of this life-threatening infection, a majority of patients will not return to their previous neurologic baseline, indicating the need for further research efforts aimed at improving the long-term sequelae.

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“…associated with susceptibility to a variety of different pathogens. However, recently, several PID have been described that are characterized by an increased frequency of infections caused by selected pathogens such as mycobacteria, pneumococci [3] and herpes simplex virus [4,5]. Such "holes-in-the-repertoire" defects (for recent review see [6]) are likely to be common in the population and may, taken together, account for a substantial number of, hitherto largely undiagnosed, patients with PID.…”

Section: Introductionmentioning

confidence: 99%

Antibody deficiency diseases

Pan‐Hammarström

Hammarström

2008

Eur J Immunol

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Primary immunodeficiency diseases are rare disorders characterized by quantitative or qualitative defects in cells or components in the immune system, resulting in a high degree of susceptibility to various types of infections. During differentiation, stem cells undergo a series of discrete steps, governed by a large number of different genes. Mutations/deletions in these genes will result in a block in differentiation of the affected cell lineage(s), leading to immunodeficiency. To date, more than 150 different types of disorders have been described. In this review, we will focus on novel findings in antibody deficiency syndromes. IntroductionPrimary immunodeficiency diseases (PID) are disorders characterized by quantitative or qualitative defects in cells or components in the immune system, resulting in a high degree of susceptibility to various types of infections. During differentiation, stem cells undergo a series of discrete steps, governed by a large number of different genes. Mutations/deletions in these genes will result in a block in differentiation of the affected cell lineage(s), leading to immunodeficiency. To date, more than 150 different types of diseases have been described and the genetic basis for most of these defects is known (see [1,2] for recent reviews).Principally, PID can be subdivided into T cell, B cell, combined (T+B), phagocyte and complement defects. The combined immunodeficiencies (SCID) are clinically the most severe and will, if undiagnosed, lead to death of the affected child, usually within the first year of life. Other defects, numerically more prevalent and including common variable immunodeficiency (CVID) and IgA deficiency (IgAD), will result in considerable morbidity, but are rarely associated with mortality.The above defects are all "global", i.e. associated with susceptibility to a variety of different pathogens. However, recently, several PID have been described that are characterized by an increased frequency of infections caused by selected pathogens such as mycobacteria, pneumococci [3] and herpes simplex virus [4,5]. Such "holes-in-the-repertoire" defects (for recent review see [6]) are likely to be common in the population and may, taken together, account for a substantial number of, hitherto largely undiagnosed, patients with PID. Furthermore, a recent observation [7] shows that novel mutations in "classical" genes, i.e. those known to be involved in a given PID, may give rise to a different phenotype, suggesting that the field is getting more complex than previously recognized. In addition, the etiology of several phenotypically similar, albeit in some cases not entirely identical, PID have recently been shown to be caused by mutations in other genes than those originally implicated (examples include hyper-IgM (HIGM, see below), X-linked lymphoproliferative syndrome [8], hyper-IgE [9, 10], Omenn syndrome [11] and X-linked susceptibility to mycobacterial infections [12]. Differences in glycosylation pattern may also account for selected disease phenotypes [13] and...

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TLR3 Deficiency in Patients with Herpes Simplex Encephalitis

Cited by 1,000 publications

References 38 publications

Evaluating the role of Toll-like receptors in diseases of the central nervous system

Evaluating the role of Toll-like receptors in diseases of the central nervous system

Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management

Antibody deficiency diseases

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