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TLR agonist

Erika Vacchelli, Norma Bloy, Fernando Aranda, Aitziber Buqué, Isabelle Cremer, Sandra Demaria, Alexander Eggermont, Silvia Chiara Formenti, Wolf Hervé Fridman, Jitka Fucikova, Jérôme Galon, Radek Spisek, Eric Tartour, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
Malignant cells succumbing to some forms of radiation therapy are particularly immunogenic and hence can initiate a therapeutically relevant adaptive immune response. This reflects the intrinsic antigenicity of malignant cells (which often synthesize a high number of potentially reactive neo-antigens) coupled with the ability of radiation therapy to boost the adjuvanticity of cell death as it stimulates the release of endogenous adjuvants from dying cells. Thus, radiation therapy has been intensively investigated for its capacity to improve the therapeutic profile of several anticancer immunotherapies, including (but not limited to) checkpoint blockers, anticancer vaccines, oncolytic viruses, Toll-like receptor (TLR) agonists, cytokines, and several small molecules with immunostimulatory effects...
2016: Oncoimmunology
Sreya Bagchi, Sha Li, Chyung-Ru Wang
Adoptive immunotherapy for cancer treatment is an emerging field of study. Till now, several tumor-derived, peptide-specific T cell responses have been harnessed for treating cancers. However, the contribution of lipid-specific T cells in tumor immunity has been understudied. CD1 molecules, which present self- and foreign lipid antigens to T cells, are divided into group 1 (CD1a, CD1b, and CD1c) and group 2 (CD1d). Although the role of CD1d-restricted natural killer T cells (NKT) in several tumor models has been well established, the contribution of group 1 CD1-restricted T cells in tumor immunity remains obscure due to the lack of group 1 CD1 expression in mice...
2016: Oncoimmunology
Sudhir Gupta, Sudhanshu Agrawal, Sastry Gollapudi, Hiromi Kubagawa
IgMFcR (FcμR) are expressed on B cell and B cell subsets. Mice deficient in secreted IgM and FcμR share properties of impaired specific antibody response and autoimmunity with patient with selective IgM deficiency (SIGMD). Intravenous immunoglobulin (IGIV) regulates immune response, including modulation of IgGFc receptors. However, there are no data on the expression of FcμR in patients with SIGMD, and the effects of IGIV on FcμR. In this study, we investigated FcμR expression in naïve marginal zone (MZ), IgM memory, and class-switched memory B cells in patients with selective IgM deficiency and healthy controls...
October 14, 2016: Human Immunology
Raphaela Mayerhofer, Esther E Fröhlich, Florian Reichmann, Aitak Farzi, Nora Kogelnik, Eleonore Fröhlich, Wolfgang Sattler, Peter Holzer
Microbial metabolites are known to affect immune system, brain, and behavior via activation of pattern recognition receptors such as Toll-like receptor 4 (TLR4). Unlike the effect of the TLR4 agonist lipopolysaccharide (LPS), the role of other TLR agonists in immune-brain communication is insufficiently understood. We therefore hypothesized that the TLR2 agonist lipoteichoic acid (LTA) causes immune activation in the periphery and brain, stimulates the hypothalamic-pituitary-adrenal (HPA) axis and has an adverse effect on blood-brain barrier (BBB) and emotional behavior...
October 14, 2016: Brain, Behavior, and Immunity
Keun Ah Ryu, Katarzyna Slowinska, Troy Moore, Aaron Esser-Kahn
We report immune response modulation with linked Toll-like receptor (TLR) agonists. Conjugating two agonists of synergistic TLRs induce an increase in immune activity compared to equal molarity of soluble agonists. Additionally, varying the distance between the agonists by changing the linker length alters the level of macrophage NF-κB activity as well as primary bone marrow derived dendritic cell IL-6 production. This modulation is effected by the size of the agonists and the pairing of the stimulated TLRs...
October 17, 2016: ACS Chemical Biology
Darlene A Monlish, Sima T Bhatt, Laura G Schuettpelz
Toll-like receptors (TLRs) are a family of pattern recognition receptors that shape the innate immune system by identifying pathogen-associated molecular patterns and host-derived damage-associated molecular patterns. TLRs are widely expressed on both immune cells and non-immune cells, including hematopoietic stem and progenitor cells, effector immune cell populations, and endothelial cells. In addition to their well-known role in the innate immune response to acute infection or injury, accumulating evidence supports a role for TLRs in the development of hematopoietic and other malignancies...
2016: Frontiers in Immunology
Nargis Khan, Susanta Pahari, Aurobind Vidyarthi, Mohammad Aqdas, Javed N Agrewala
Tuberculosis (TB) is the leading cause of morbidity and mortality among all infectious diseases. Failure of Bacillus Calmette Guerin as a vaccine and serious side-effects and toxicity due to long-term TB drug regime are the major hurdles associated with TB control. The problem is further compounded by the emergence of drug-resistance strains of Mycobacterium tuberculosis (Mtb). Consequently, it demands a serious attempt to explore safer and superior treatment approaches. Recently, an improved understanding of host-pathogen interaction has opened up new avenues for immunotherapy for treating TB...
2016: Frontiers in Immunology
Hongbin Jia, Shuangshuang Xu, Qingzhen Liu, Jian Liu, Jianguo Xu, Weiyan Li, Yi Jin, Qing Ji
The molecular mechanisms underlying neuropathic pain have yet to be elucidated. The present study aimed to examine the modulation of neuroimmune activation in the spinal cord by the synthetic peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, pioglitazone (Pio), in a rat model of neuropathic pain induced by chronic constriction injury (CCI). Rats were randomly assigned into four groups: Sham surgery with vehicle, chronic constriction injury with vehicle or Pio (10 mg/kg), and chronic constriction injury with Pio and a PPAR-γ antagonist GW9662 (2 mg/kg)...
October 2016: Experimental and Therapeutic Medicine
Nancy Gupta, Satish Vedi, Dennis Y Kunimoto, Babita Agrawal, Rakesh Kumar
Mycobacterium tuberculosis (Mtb), the bacterial cause of tuberculosis, is a leading infectious agent worldwide. The development of a new vaccine against Mtb is essential to control global spread of tuberculosis, since the current vaccine BCG is not very effective and antibiotic resistance is a serious, burgeoning problem. ESAT-6 is a secreted protein of Mtb, which is absent in BCG but has been implicated in inducing protective immunity against Mtb. Peptide based subunit vaccines are attractive due to their safety and high specificity in eliciting immune responses, but small synthetic peptides are usually not very immunogenic...
September 29, 2016: Vaccine
Romy E Verbeek, Peter D Siersema, Frank P Vleggaar, Fiebo J Ten Kate, George Posthuma, Rhonda F Souza, Judith de Haan, Jantine W P M van Baal
BACKGROUND AND AIMS: Inflammation plays an important role in the development of esophageal adenocarcinoma and its metaplastic precursor lesion, Barrett's esophagus. Toll-like receptor (TLR) 2 signalling and lysosomal function have been linked to inflammation-associated carcinogenesis. We examined the expression of TLR2 in the esophagus and the effect of long-term TLR2 activation on morphological changes and expression of factors involved in lysosomal function in a Barrett's esophagus epithelium cell line...
September 2016: Journal of Gastrointestinal and Liver Diseases: JGLD
Kyoung-Ho Pyo, You-Won Lee, Sun Min Lim, Eun-Hee Shin
Profilin-like protein in Toxoplasma gondii (TgPLP) is a Toll-like receptor (TLR) agonist. In this study, we investigated whether TgPLP has an adjuvant effect on immune function in autologous whole-tumor-cell vaccine (AWV) treatment. Mice vaccinated with AWV together with recombinant TgPLP protein had smaller CT26 tumors and increased survival. TgPLP treatment strongly increased the production of IL-12 through MyD88 signaling and several chemokines, including CCL5, CCL12, and XCL1, in bone marrow-derived macrophages (BMMs)...
September 28, 2016: Oncotarget
Jonathan Laiño, Julio Villena, Paulraj Kanmani, Haruki Kitazawa
Researchers have demonstrated that lactic acid bacteria (LAB) with immunomodulatory capabilities (immunobiotics) exert their beneficial effects through several molecules, including cell wall, peptidoglycan, and exopolysaccharides (EPS), that are able to interact with specific host cell receptors. EPS from LAB show a wide heterogeneity in its composition, meaning that biological properties depend on the strain and. therefore, only a part of the mechanism of action has been elucidated for these molecules. In this review, we summarize the current knowledge of the health-promoting actions of EPS from LAB with special focus on their immunoregulatory actions...
August 15, 2016: Microorganisms
Lydia Dyck, Mieszko M Wilk, Mathilde Raverdeau, Alicja Misiak, Louis Boon, Kingston H G Mills
The co-inhibitory molecule PD-1 suppresses T cell responses and has been targeted in the treatment of cancer. Here, we examined the role of PD-1 in regulating the balance between regulatory and effector T cells and whether blocking PD-1 could enhance tumour vaccine-induced protective immunity. A significantly higher proportion of tumour-resident T cells expressed PD-1 and Foxp3 compared with T cells in the tumour circulation or draining lymph nodes, and this correlated with a lower frequency of IFN-γ- and TNF-secreting CD8 T cells...
September 28, 2016: Cancer Immunology, Immunotherapy: CII
Frédérique Larousserie, Laura Bsiri, Valérie Dumaine, Céline Dietrich, Anne Audebourg, Brigitte Radenen-Bussière, Philippe Anract, Marie-Cécile Vacher-Lavenu, Odile Devergne
IL-27 regulates immune responses as well as hematopoiesis and bone remodeling, but its cellular sources in the bone remain unknown. In this study, we investigated whether osteoclasts and osteoblasts-the 2 cell types orchestrating bone homeostasis-could be a source of IL-27 and identified stimuli that induce its expression in vitro. We observed that human monocyte-derived osteoclasts expressed a broader range of TLRs than did human primary osteoblasts and that both cell types exhibited a differential induction of IL-27 expression in response to TLR or cytokine stimulation...
September 27, 2016: Journal of Leukocyte Biology
Wei Hseun Yeap, Kok Loon Wong, Noriko Shimasaki, Esmeralda Chi Yuan Teo, Jeffrey Kim Siang Quek, Hao Xiang Yong, Colin Phipps Diong, Antonio Bertoletti, Yeh Ching Linn, Siew Cheng Wong
Antibody-dependent cellular cytotoxicity (ADCC) is exerted by immune cells expressing surface Fcγ receptors (FcγRs) against cells coated with antibody, such as virus-infected or transformed cells. CD16, the FcγRIIIA, is essential for ADCC by NK cells, and is also expressed by a subset of human blood monocytes. We found that human CD16- expressing monocytes have a broad spectrum of ADCC capacities and can kill cancer cell lines, primary leukemic cells and hepatitis B virus-infected cells in the presence of specific antibodies...
September 27, 2016: Scientific Reports
Yang Xu, Hongxia Dong, Changhui Ge, Yan Gao, Haifeng Liu, Weiguang Li, Chenggang Zhang
BACKGROUND: Ulcerative colitis (UC) is a nonspecific inflammatory disease for which medications and therapeutic strategies have only been moderately successful. CBLB502, a toll-like receptor 5 (TLR5) agonist derived from Salmonella flagellin, exhibits anticancer and radioprotective activities via modulation of TLRs and the nuclear factor kappa B (NF-κB) signaling pathway and can protect against acute renal ischemic failure. In this study, we intend to examine the effects of CBLB502 on both TLR responses and the interleukin (IL) and NF-κB signaling pathways in UC treatment...
August 2016: Annals of Translational Medicine
A Głobińska, M Pawełczyk, A Piechota-Polańczyk, A Olszewska-Ziąber, S Moskwa, A Mikołajczyk, A Jabłońska, P Zakrzewski, M Brauncajs, M Jarzębska, S Taka, N G Papadopoulos, M L Kowalski
PURPOSE: The aim of the study was to assess the immune response to parainfluenza virus type 3 (PIV3), rhinovirus 1B (RV1B) and intracellular Toll-like receptors (TLR) agonists in nasal epithelial cells (NECs) from patients with allergic rhinitis and healthy controls. METHODS: NECs were obtained from 8 patients with allergic rhinitis (AR) and 11 non-atopic healthy controls (HC) by nasal scraping, grown to confluence and exposed to PIV3, RV1B infection or TLR3 and TLR7/8 agonists...
September 26, 2016: Clinical and Experimental Immunology
Rafiou Agoro, Catherine Mura
Iron is essential in all organisms. In mammals systemic iron homeostasis relies on hepcidin, a peptide hormone with defensin properties, and its target, the cell iron exporter ferroportin. Hepcidin and ferroportin transcription are both upregulated by high iron levels, but are inversely regulated upon inflammation, leading to hypoferremia. Thus, host iron genes regulation may affect the innate immune responses against infectious microorganisms. Since macrophages, which are crucial innate immune cells, express both hepcidin and ferroportin, we explored in these cells their transcriptional regulation upon inflammation which is not completely understood...
October 2016: Blood Cells, Molecules & Diseases
Robert G Schaut, Tara L Grinnage-Pulley, Kevin J Esch, Angela J Toepp, Malcolm S Duthie, Randall F Howard, Steven G Reed, Christine A Petersen
Visceral leishmaniasis (VL), caused by infection with the obligate intracellular protozoan parasite Leishmania infantum, is a fatal disease of dogs and humans. Protection against VL requires a T helper 1 (Th1) skewed CD4(+) T response, but despite this knowledge, there are currently no approved-to-market vaccines for humans and only three veterinary-use vaccines globally. As VL progresses from asymptomatic to symptomatic, L. infantum-specific interferon gamma (IFNγ) driven-Th1 responses become dampened and a state of immune exhaustion established...
October 17, 2016: Vaccine
Sukriti Sukriti, Nirupma Trehanpati, Manoj Kumar, Chandana Pande, Syed S Hissar, Shiv Kumar Sarin
BACKGROUND: Dendritic cells (DCs) promote pathogen recognition, uptake and presentation of antigen through DC-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) and toll-like receptors (TLRs). AIMS AND OBJECTIVES: We aimed to study temporal changes in DCs, TLRs and DC-SIGN during acute viral hepatitis B (AVHB) infection and compare them to chronic (CHB) and to investigate the earliest time point of activated pathogen recognition receptors in hepatitis B viral infection...
September 22, 2016: Hepatology International
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