Liver X receptor agonism promotes articular inflammation in murine collagen-induced arthritis.
AuthorsAsquith DL, Miller AM, Hueber AJ, McKinnon HJ, Sattar N, Graham GJ, McInnes IB,
JournalArthritis Rheum
PubMed ID19714646
Liver X receptors (LXRs) have previously been implicated in the regulation of inflammation and have, in general, been ascribed an antiinflammatory role. This study was therefore undertaken to explore the biologic mechanisms of LXRs in vivo and in vitro in an experimental inflammatory arthritis model. Male DBA/1 mice were immunized ... More
Mouse-passaged severe acute respiratory syndrome-associated coronavirus leads to lethal pulmonary edema and diffuse alveolar damage in adult but not young mice.
AuthorsNagata N, Iwata N, Hasegawa H, Fukushi S, Harashima A, Sato Y, Saijo M, Taguchi F, Morikawa S, Sata T
JournalAm J Pathol
PubMed ID18467696
'Advanced age is a risk factor of severe acute respiratory syndrome (SARS) in humans. To understand its pathogenesis, we developed an animal model using BALB/c mice and the mouse-passaged Frankfurt 1 isolate of SARS coronavirus (SARS-CoV). We examined the immune responses to SARS-CoV in both young and adult mice. SARS-CoV ... More
Intranasal administration of poly(I:C) and LPS in BALB/c mice induces airway hyperresponsiveness and inflammation via different pathways.
AuthorsStarkhammar M, Kumlien Georén S, Swedin L, Dahlén SE, Adner M, Cardell LO,
JournalPLoS One
PubMed ID22355412
'Bacterial and viral infections are known to promote airway hyperresponsiveness (AHR) in asthmatic patients. The mechanism behind this reaction is poorly understood, but pattern recognizing Toll-like receptors (TLRs) have recently been suggested to play a role. To explore the relation between infection-induced airway inflammation and the development of AHR, poly(I:C) ... More
Microfilariae of the filarial nematode Litomosoides sigmodontis exacerbate the course of lipopolysaccharide-induced sepsis in mice.
AuthorsHübner MP, Pasche B, Kalaydjiev S, Soboslay PT, Lengeling A, Schulz-Key H, Mitre E, Hoffmann WH
JournalInfect Immun
PubMed ID18250172
'Helminths facilitate their own survival by actively modulating the immune systems of their hosts. We investigated the impacts that different life cycle stages of the rodent filaria Litomosoides sigmodontis have on the inflammatory responses of mice injected with sublethal doses of lipopolysaccharide (LPS). Mice infected with female adult worms from ... More
IL-33 exacerbates antigen-induced arthritis by activating mast cells.
AuthorsXu D, Jiang HR, Kewin P, Li Y, Mu R, Fraser AR, Pitman N, Kurowska-Stolarska M, McKenzie AN, McInnes IB, Liew FY
JournalProc Natl Acad Sci U S A
PubMed ID18667700
'IL-33, a cytokine of the IL-1 family, is closely associated with type II T cell responses. Here, we report an unexpected proinflammatory role of IL-33 in inflammatory arthritis. IL-33 was expressed in synovial fibroblasts from patients with rheumatoid arthritis (RA). Expression was markedly elevated in vitro by inflammatory cytokines. Mice ... More
Prophylactic effects of chitin microparticles on highly pathogenic H5N1 influenza virus.
AuthorsIchinohe T, Nagata N, Strong P, Tamura S, Takahashi H, Ninomiya A, Imai M, Odagiri T, Tashiro M, Sawa H, Chiba J, Kurata T, Sata T, Hasegawa H,
JournalJ Med Virol
PubMed ID17457919
'Highly pathogenic avian influenza virus (H5N1) is an emerging pathogen with the potential to cause great harm to humans, and there is concern about the potential for a new influenza pandemic. This virus is resistant to the antiviral effects of interferons and tumor necrosis factor-alpha. However, the mechanism of interferon-independent ... More
MyD88-dependent signals are essential for the host immune response in experimental brain abscess.
AuthorsKielian T, Phulwani NK, Esen N, Syed MM, Haney AC, McCastlain K, Johnson J,
JournalJ Immunol
PubMed ID17372011
'Brain abscesses form in response to a parenchymal infection by pyogenic bacteria, with Staphylococcus aureus representing a common etiologic agent of human disease. Numerous receptors that participate in immune responses to bacteria, including the majority of TLRs, the IL-1R, and the IL-18R, use a common adaptor molecule, MyD88, for transducing ... More
Alpha/beta interferon receptor signaling amplifies early proinflammatory cytokine production in the lung during respiratory syncytial virus infection.
AuthorsGoritzka M, Durant LR, Pereira C, Salek-Ardakani S, Openshaw PJ, Johansson C,
Journal
PubMed ID24648449
'Type I interferons (IFNs) are produced early upon virus infection and signal through the alpha/beta interferon (IFN-a/ß) receptor (IFNAR) to induce genes that encode proteins important for limiting viral replication and directing immune responses. To investigate the extent to which type I IFNs play a role in the local regulation ... More
Design, synthesis and biological evaluation of novel antagonist compounds of Toll-like receptors 7, 8 and 9.
AuthorsKandimalla ER, Bhagat L, Wang D, Yu D, Sullivan T, La Monica N, Agrawal S,
JournalNucleic Acids Res
PubMed ID23396449
'Oligonucleotides containing an immune-stimulatory motif and an immune-regulatory motif act as antagonists of Toll-like receptor (TLR)7 and TLR9. In the present study, we designed and synthesized oligonucleotide-based antagonists of TLR7, 8 and 9 containing a 7-deaza-dG or arabino-G modification in the immune-stimulatory motif and 2''-O-methylribonucleotides as the immune-regulatory motif. We ... More
Depletion of autoreactive plasma cells and treatment of lupus nephritis in mice using CEP-33779, a novel, orally active, selective inhibitor of JAK2.
AuthorsLu LD, Stump KL, Wallace NH, Dobrzanski P, Serdikoff C, Gingrich DE, Dugan BJ, Angeles TS, Albom MS, Mason JL, Ator MA, Dorsey BD, Ruggeri BA, Seavey MM,
JournalJ Immunol
PubMed ID21880982
'Accumulating evidence suggests that autoreactive plasma cells play an important role in systemic lupus erythematosus (SLE). In addition, several proinflammatory cytokines promote autoreactive B cell maturation and autoantibody production. Hence, therapeutic targeting of such cytokine pathways using a selective JAK2 inhibitor, CEP-33779 (JAK2 enzyme IC(50) = 1.3 nM; JAK3 enzyme ... More
Rapamycin and IL-2 reduce lethal acute graft-versus-host disease associated with increased expansion of donor type CD4+CD25+Foxp3+ regulatory T cells.
AuthorsShin HJ, Baker J, Leveson-Gower DB, Smith AT, Sega EI, Negrin RS,
JournalBlood
PubMed ID21734238
'Previous work has demonstrated that both rapamycin (RAPA) and IL-2 enhance CD4?CD25?Foxp3? regulatory T-cell (Treg) proliferation and function in vitro. We investigated whether the combination of RAPA plus IL-2 could impact acute GVHD induction after bone marrow transplantation (BMT). RAPA plus IL-2 resulted in improved survival and a reduction in ... More
IL-33 attenuates EAE by suppressing IL-17 and IFN-? production and inducing alternatively activated macrophages.
'Interleukin (IL)-33, a member of the IL-1 cytokine family, is an important modulator of the immune system associated with several immune-mediated disorders. High levels of IL-33 are expressed by the central nervous system (CNS) suggesting a potential role of IL-33 in autoimmune CNS diseases. We have investigated the expression and ... More
Immunomodulatory role of proteinase-activated receptor-2.
'Proteinase-activated receptor-2 (PAR(2)) has been implicated in inflammatory articular pathology. Using the collagen-induced arthritis model (CIA) the authors have explored the capacity of PAR(2) to regulate adaptive immune pathways that could promote autoimmune mediated articular damage. Using PAR(2) gene deletion and other approaches to inhibit or prevent PAR(2) activation, the ... More
Low-dose paclitaxel prior to intratumoral dendritic cell vaccine modulates intratumoral cytokine network and lung cancer growth.
AuthorsZhong H, Han B, Tourkova IL, Lokshin A, Rosenbloom A, Shurin MR, Shurin GV
JournalClin Cancer Res
PubMed ID17875775
'The main goal of this study was to provide the "proof-of-principle" that low-dose paclitaxel is able to change the tumor microenvironment and improve the outcome of intratumoral dendritic cell vaccine in a murine lung cancer model.' ... More
Novel, orally active, proteasome inhibitor, delanzomib (CEP-18770), ameliorates disease symptoms and glomerulonephritis in two preclinical mouse models of SLE.
AuthorsSeavey MM, Lu LD, Stump KL, Wallace NH, Ruggeri BA,
JournalInt Immunopharmacol
PubMed ID22178195
'Current therapies for late-stage systemic lupus erythematosus (SLE) are limited to cytotoxic agents. Delanzomib (CEP-18770) is an orally active, reversible P2 threonine boronic acid inhibitor of the 26S mammalian proteasome. Delanzomib was tested in a head-to-head comparison against bortezomib to protect and treat mice with fatal lupus nephritis (LN). Age ... More
AuthorsQiao H, Sonoda KH, Ikeda Y, Yoshimura T, Hijioka K, Jo YJ, Sassa Y, Tsutsumi-Miyahara C, Hata Y, Akira S, Ishibashi T
JournalJ Leukoc Biol
PubMed ID17234681
'Recently, the proinflammatory cytokine IL-18 has been shown to have a role in angiogenesis. This study aimed to elucidate its role in abnormal neovascularization (NV) in an oxygen-induced retinopathy (OIR) mouse model of the retinopathy seen in human premature newborns. IL-18 was constitutively expressed in the retina in C57BL/6 mice, ... More
Diminished inflammatory responses to natural pneumovirus infection among older mice.
AuthorsBonville CA, Bennett NJ, Percopo CM, Branigan PJ, Del Vecchio AM, Rosenberg HF, Domachowske JB,
JournalVirology
PubMed ID17655904
'Immune responses to virus infection undergo significant change as part of the aging process. Here we examine the inflammatory responses of older, but otherwise immunologically naive mice to infection with pneumonia virus of mice (PVM). Although we see no changes in the extent or kinetics of virus replication, we observe ... More
Hepatic stellate cells undermine the allostimulatory function of liver myeloid dendritic cells via STAT3-dependent induction of IDO.
AuthorsSumpter TL, Dangi A, Matta BM, Huang C, Stolz DB, Vodovotz Y, Thomson AW, Gandhi CR,
JournalJ Immunol
PubMed ID22962681
'Hepatic stellate cells (HSCs) are critical for hepatic wound repair and tissue remodeling. They also produce cytokines and chemokines that may contribute to the maintenance of hepatic immune homeostasis and the inherent tolerogenicity of the liver. The functional relationship between HSCs and the professional migratory APCs in the liver, that ... More
MyD88 expression by CNS-resident cells is pivotal for eliciting protective immunity in brain abscesses.
AuthorsGarg S, Nichols JR, Esen N, Liu S, Phulwani NK, Syed MM, Wood WH, Zhang Y, Becker KG, Aldrich A, Kielian T,
JournalASN Neuro
PubMed ID19570030
'MyD88 KO (knockout) mice are exquisitely sensitive to CNS (central nervous system) infection with Staphylococcus aureus, a common aetiological agent of brain abscess, exhibiting global defects in innate immunity and exacerbated tissue damage. However, since brain abscesses are typified by the involvement of both activated CNS-resident and infiltrating immune cells, ... More
Reduced levels of protein tyrosine phosphatase CD45 protect mice from the lethal effects of Ebola virus infection.
AuthorsPanchal RG, Bradfute SB, Peyser BD, Warfield KL, Ruthel G, Lane D, Kenny TA, Anderson AO, Raschke WC, Bavari S,
JournalCell Host Microbe
PubMed ID19683682
'Ebola virus (EBOV) infection of humans is a lethal but accidental dead-end event. Understanding resistance to EBOV in other species may help establish the basis of susceptibility differences among its hosts. Although rodents are resistant to EBOV, a murine-adapted variant is lethal when injected intraperitoneally into mice. We find that ... More
Blockade of lymphotoxin-beta receptor signaling reduces aspects of Sjögren's syndrome in salivary glands of non-obese diabetic mice.
'The lymphotoxin-beta receptor (LTbetaR) pathway is important in the development and maintenance of lymphoid structures. Blocking this pathway has proven beneficial in murine models of autoimmune diseases such as diabetes and rheumatoid arthritis. The aim of this study was to determine the effects of LTbetaR pathway blockade on Sjögren syndrome ... More
Involvement of Th17 cells and the effect of anti-IL-6 therapy in autoimmune uveitis.
AuthorsYoshimura T, Sonoda KH, Ohguro N, Ohsugi Y, Ishibashi T, Cua DJ, Kobayashi T, Yoshida H, Yoshimura A,
JournalRheumatology (Oxford)
PubMed ID19164426
'Human endogenous uveitis is one of the sight-threatening diseases associated with variety of systemic disorders, such as Behcet''s disease and sarcoidosis. Recently, biosynthesized antibodies against inflammatory cytokines have been recognized to be useful to control the regional inflammation. In this study, we focused on the possibility of IL-6-based biological therapies ... More
A strain of Lactobacillus casei inhibits the effector phase of immune inflammation.
AuthorsSchiffer C, Lalanne AI, Cassard L, Mancardi DA, Malbec O, Bruhns P, Dif F, Daëron M,
JournalJ Immunol
PubMed ID21810608
Some nonpathogenic bacteria were found to have protective effects in mouse models of allergic and autoimmune diseases. These
Microbiologic and immunologic evaluation of a single high dose of azithromycin for treatment of experimental Mycoplasma pneumoniae pneumonia.
AuthorsRíos AM, Fonseca-Aten M, Mejías A, Chávez-Bueno S, Katz K, Gómez AM, McCracken GH, Ramilo O, Hardy RD,
JournalAntimicrob Agents Chemother
PubMed ID16127085
We evaluated the efficacy of azithromycin therapy given as a single high dose or divided over 5 days for the treatment of mild experimental Mycoplasma pneumoniae pneumonia. Although both azithromycin regimens significantly reduced quantitative cultures, lung histopathology, and pulmonary cytokines and chemokines, there were no significant differences between the two ... More
Variation in colonization, ADP-ribosylating and vacuolating cytotoxin, and pulmonary disease severity among mycoplasma pneumoniae strains.
Mycoplasma pneumoniae was recently discovered to produce an ADP-ribosylating and vacuolating cytotoxin, designated CARDS toxin, which is hypothesized to be a primary pathogenic mechanism responsible for M. pneumoniae-induced pulmonary inflammation. It is unknown if cytotoxin production varies with M. pneumoniae strain or if variation in cytotoxin production affects pulmonary disease ... More
A critical function for CD200 in lung immune homeostasis and the severity of influenza infection.
AuthorsSnelgrove RJ, Goulding J, Didierlaurent AM, Lyonga D, Vekaria S, Edwards L, Gwyer E, Sedgwick JD, Barclay AN, Hussell T,
JournalNat Immunol
PubMed ID18660812
The lung must maintain a high threshold of immune 'ignorance' to innocuous antigens to avoid inflammatory disease that depends on the balance of positive inflammatory signals and repressor pathways. We demonstrate here that airway macrophages had higher expression of the negative regulator CD200 receptor (CD200R) than did their systemic counterparts. ... More
Greatly improved survival and neuroprotection in aquaporin-4-knockout mice following global cerebral ischemia.
Aquaporin-4 (AQP4), the principal water channel in astrocytes, is involved in brain water movement, inflammation, and neuroexcitation. In this study, there was strong neuroprotection in mice lacking AQP4 in a model of global cerebral ischemia produced by transient, bilateral carotid artery occlusion (BCAO). Survival and neurological outcome were greatly improved ... More
Selective expansion of allogeneic regulatory T cells by hepatic stellate cells: role of endotoxin and implications for allograft tolerance.
AuthorsDangi A, Sumpter TL, Kimura S, Stolz DB, Murase N, Raimondi G, Vodovotz Y, Huang C, Thomson AW, Gandhi CR,
JournalJ Immunol
PubMed ID22427640
Hepatic stellate cells (HSCs) may play an important role in hepatic immune regulation by producing numerous cytokines/chemokines and expressing Ag-presenting and T cell coregulatory molecules. Due to disruption of the endothelial barrier during cold-ischemic storage and reperfusion of liver grafts, HSCs can interact directly with cells of the immune system. ... More
TLR7 and TLR9 trigger distinct neuroinflammatory responses in the CNS.
AuthorsButchi NB, Woods T, Du M, Morgan TW, Peterson KE,
JournalAm J Pathol
PubMed ID21801870
Toll-like receptors (TLRs) 7 and 9 recognize nucleic acid determinants from viruses and bacteria and elicit the production of type I interferons and proinflammatory cytokines. TLR7 and TLR9 are similar regarding localization and signal transduction mechanisms. However, stimulation of these receptors has differing effects in modulating viral pathogenesis and in ... More
Induction of osteoarthritis and metabolic inflammation by a very high-fat diet in mice: effects of short-term exercise.
AuthorsGriffin TM, Huebner JL, Kraus VB, Yan Z, Guilak F,
JournalArthritis Rheum
PubMed ID21953366
To test the hypotheses that obesity due to a very high-fat diet induces knee osteoarthritis (OA), and that short-term wheel-running exercise protects against obesity-induced knee OA by reducing systemic inflammation and metabolic dysregulation. Male C57BL/6J mice were fed either a control diet (13.5% kcal from fat) or a very high-fat ... More
Expression and detrimental role of hematopoietic prostaglandin D synthase in spinal cord contusion injury.
AuthorsRedensek A, Rathore KI, Berard JL, López-Vales R, Swayne LA, Bennett SA, Mohri I, Taniike M, Urade Y, David S,
JournalGlia
PubMed ID21294159
Prostaglandin D(2) (PGD(2) ) is a potent inflammatory mediator, which is implicated in both the initiation and resolution of inflammation in peripheral non-neural tissues. Its role in the central nervous system has not been fully elucidated. Spinal cord injury (SCI) is associated with an acute inflammatory response, which contributes to ... More
Extracellular administration of BCL2 protein reduces apoptosis and improves survival in a murine model of sepsis.
AuthorsIwata A, de Claro RA, Morgan-Stevenson VL, Tupper JC, Schwartz BR, Liu L, Zhu X, Jordan KC, Winn RK, Harlan JM,
JournalPLoS One
PubMed ID21390214
Severe sepsis and septic shock are major causes of morbidity and mortality worldwide. In experimental sepsis there is prominent apoptosis of various cell types, and genetic manipulation of death and survival pathways has been shown to modulate organ injury and survival. We investigated the effect of extracellular administration of two ... More
Induction of autoantibodies against lung matrix proteins and smoke-induced inflammation in mice.
AuthorsBrandsma CA, Timens W, Geerlings M, Jekel H, Postma DS, Hylkema MN, Kerstjens HA,
JournalBMC Pulm Med
PubMed ID21144028
Smoking is the major etiologic factor in COPD, yet the exact underlying pathogenetic mechanisms have not been elucidated. Since a few years, there is mounting evidence that a specific immune response, partly present as an autoimmune response, contributes to the pathogenesis of COPD. Increased levels of anti-Hep-2 epithelial cell and ... More
Inflammatory changes in the airways of mice caused by cigarette smoke exposure are only partially reversed after smoking cessation.
Tobacco smoking irritates and damages the respiratory tract and contributes to a higher risk of developing lung emphysema. At present, smoking cessation is the only effective treatment for reducing the progression of lung emphysema, however, there is hardly anything known about the effects of smoking cessation on cytokine and chemokine ... More
IL-33 amplifies the polarization of alternatively activated macrophages that contribute to airway inflammation.
AuthorsKurowska-Stolarska M, Stolarski B, Kewin P, Murphy G, Corrigan CJ, Ying S, Pitman N, Mirchandani A, Rana B, van Rooijen N, Shepherd M, McSharry C, McInnes IB, Xu D, Liew FY,
JournalJ Immunol
PubMed ID19841166
Alternatively activated macrophages (AAM) play a crucial role in type 2 immunity. Mice deficient in ST2, a receptor for the latest member of the IL-1 family, IL-33, have impaired type 2 immune responses. We therefore reasoned that IL-33/ST2 signaling may be involved in the differentiation and activation of AAM during ... More
Development and characterization of a mouse model for Marburg hemorrhagic fever.
AuthorsWarfield KL, Bradfute SB, Wells J, Lofts L, Cooper MT, Alves DA, Reed DK, VanTongeren SA, Mech CA, Bavari S,
JournalJ Virol
PubMed ID19369350
The lack of a mouse model has hampered an understanding of the pathogenesis and immunity of Marburg hemorrhagic fever (MHF), the disease caused by marburgvirus (MARV), and has created a bottleneck in the development of antiviral therapeutics. Primary isolates of the filoviruses, i.e., ebolavirus (EBOV) and MARV, are not lethal ... More
Ligand up-regulation does not correlate with a role for CCR1 in pathogenesis in a mouse model of non-lymphocyte-mediated neurological disease.
AuthorsCorbin ME, Pourciau S, Morgan TW, Boudreaux M, Peterson KE,
JournalJ Neurovirol
PubMed ID16966215
CCR1 ligands, including CCL3, CCL5, and CCL7, are up-regulated in a number of neurological disorders in humans and animal models. CCR1 is expressed by multiple cell types in the central nervous system (CNS), suggesting that receptor signaling by neuronal cell types may influence pathogenesis. In the current study, the authors ... More
ES-62, an immunomodulator secreted by filarial nematodes, suppresses clonal expansion and modifies effector function of heterologous antigen-specific T cells in vivo.
AuthorsMarshall FA, Grierson AM, Garside P, Harnett W, Harnett MM,
JournalJ Immunol
PubMed ID16237074
ES-62 is a phosphorylcholine-containing glycoprotein secreted by filarial nematodes, which has previously been shown to possess a range of immunomodulatory capabilities. We now show, using a CD4+ transgenic TCR T cell adoptive transfer system, that ES-62 can modulate heterologous Ag (OVA)-specific responses in vivo. Thus, in contrast to the mixed ... More
Carbon nanotubes enhance CpG uptake and potentiate antiglioma immunity.
AuthorsZhao D, Alizadeh D, Zhang L, Liu W, Farrukh O, Manuel E, Diamond DJ, Badie B,
JournalClin Cancer Res
PubMed ID21088258
Stimulation of toll-like receptor-9 (TLR9) by CpG oligodeoxynucleotides (CpG) has been shown to counteract the immunosuppressive microenvironment and to inhibit tumor growth in glioma models. Because TLR9 is located intracellularly, we hypothesized that methods that enhance its internalization may also potentiate its immunostimulatory response. The goal of this study was ... More
Drug-selected human lung cancer stem cells: cytokine network, tumorigenic and metastatic properties.
AuthorsLevina V, Marrangoni AM, DeMarco R, Gorelik E, Lokshin AE,
JournalPLoS One
PubMed ID18728788
Cancer stem cells (CSCs) are thought to be responsible for tumor regeneration after chemotherapy, although direct confirmation of this remains forthcoming. We therefore investigated whether drug treatment could enrich and maintain CSCs and whether the high tumorogenic and metastatic abilities of CSCs were based on their marked ability to produce ... More
Analysis of the neuroinflammatory response to TLR7 stimulation in the brain: comparison of multiple TLR7 and/or TLR8 agonists.
AuthorsButchi NB, Pourciau S, Du M, Morgan TW, Peterson KE
JournalJ Immunol
PubMed ID18490763
Activation of astrocytes and microglia and the production of proinflammatory cytokines and chemokines are often associated with virus infection in the CNS as well as a number of neurological diseases of unknown etiology. These inflammatory responses may be initiated by recognition of pathogen-associated molecular patterns (PAMPs) that stimulate TLRs. TLR7 ... More
The lineage-c-Kit+Sca-1+ cell response to Escherichia coli bacteremia in Balb/c mice.
AuthorsZhang P, Nelson S, Bagby GJ, Siggins R, Shellito JE, Welsh DA
JournalStem Cells
PubMed ID18483422
During bacterial infection, the bone marrow hematopoietic activity shifts toward granulocyte production, which is critical for host defenses. Along with this enhancement of granulopoiesis, the bone marrow also increases its release of hematopoietic precursors. At the present time, little is known about the commitment of hematopoietic precursor cells, including hematopoietic ... More
Poly-thymidine oligonucleotides mediate activation of murine glial cells primarily through TLR7, not TLR8.
AuthorsDu M, Butchi NB, Woods T, Peterson KE
JournalPLoS One
PubMed ID21811614
The functional role of murine TLR8 in the inflammatory response of the central nervous system (CNS) remains unclear. Murine TLR8 does not appear to respond to human TLR7/8 agonists, due to a five amino acid deletion in the ectodomain. However, recent studies have suggested that murine TLR8 may be stimulated ... More