scholarly journals The Immune Response toTrypanosoma cruzi: Role of Toll-Like Receptors and Perspectives for Vaccine Development

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Mauricio M. Rodrigues ◽  
Ana Carolina Oliveira ◽  
Maria Bellio
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Vaccine Development ◽  
State Of The Art ◽  
Toll Like Receptor ◽  
Vaccine Research ◽  
The Past ◽  
Acquired Immune Responses ◽  
Molecular Patterns

In the past ten years, studies have shown the recognition ofTrypanosoma cruzi-associated molecular patterns by members of the Toll-like receptor (TLR) family and demonstrated the crucial participation of different TLRs during the experimental infection with this parasite. In the present review, we will focus on the role of TLR-activated pathways in the modulation of both innate and acquired immune responses toT. cruziinfection, as well as discuss the state of the art of vaccine research and development against the causative agent of Chagas disease (or American trypanosomiasis).

scholarly journals Dual Role of Toll-Like Receptor 7 in the Pathogenesis of Rabies Virus in a Mouse Model

2020 ◽  
Vol 94 (9) ◽  
Author(s):  
Zhaochen Luo ◽  
Lei Lv ◽  
Yingying Li ◽  
Baokun Sui ◽  
Qiong Wu ◽  
...  
Keyword(s):  
Immune Response ◽  
Mouse Model ◽  
Immune Responses ◽  
Rabies Virus ◽  
Mouse Brain ◽  
Early Stage ◽  
Toll Like Receptor ◽  
Innate Recognition ◽  
Recognition Receptor

ABSTRACT Rabies, caused by rabies virus (RABV), is a fatal encephalitis in humans and other mammals, which continues to present a public health threat in most parts of the world. Our previous study demonstrated that Toll-like receptor 7 (TLR7) is essential in the induction of anti-RABV antibodies via the facilitation of germinal center formation. In the present study, we investigated the role of TLR7 in the pathogenicity of RABV in a mouse model. Using isolated plasmacytoid dendritic cells (pDCs), we demonstrated that TLR7 is an innate recognition receptor for RABV. When RABV invaded from the periphery, TLR7 detected viral single-stranded RNA and triggered immune responses that limited the virus’s entry into the central nervous system (CNS). When RABV had invaded the CNS, its detection by TLR7 led to the production of cytokines and chemokines and an increase the permeability of the blood-brain barrier. Consequently, peripheral immune cells, including pDCs, macrophages, neutrophils, and B cells infiltrated the CNS. While this immune response, triggered by TLR7, helped to clear viruses, it also increased neuroinflammation and caused immunopathology in the mouse brain. Our results demonstrate that TLR7 is an innate recognition receptor for RABV, which restricts RABV invasion into the CNS in the early stage of viral infection but also contributes to immunopathology by inducing neuroinflammation. IMPORTANCE Developing targeted treatment for RABV requires understanding the innate immune response to the virus because early virus clearance is essential for preventing the fatality when the infection has progressed to the CNS. Previous studies have revealed that TLR7 is involved in the immune response to RABV. Here, we establish that TLR7 recognizes RABV and facilitates the production of some interferon-stimulated genes. We also demonstrated that when RABV invades into the CNS, TLR7 enhances the production of inflammatory cytokines which contribute to immunopathology in the mouse brain. Taken together, our findings suggest that treatments for RABV must consider the balance between the beneficial and harmful effects of TLR7-triggered immune responses.

scholarly journals Distinct single-component adjuvants steer human DC-mediated T-cell polarization via Toll-like receptor signaling toward a potent antiviral immune response

2021 ◽  
Vol 118 (39) ◽  
pp. e2103651118
Author(s):  
Laura Roßmann ◽  
Katrin Bagola ◽  
Tharshana Stephen ◽  
Anna-Lisa Gerards ◽  
Bianca Walber ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Vaccine Development ◽  
Nk Cell ◽  
Checkpoint Inhibitors ◽  
Cell Polarization ◽  
Vaccine Adjuvants ◽  
Toll Like Receptor ◽  
Antiviral Immune Response ◽  
Monophosphoryl Lipid A

The COVID-19 pandemic highlights the importance of efficient and safe vaccine development. Vaccine adjuvants are essential to boost and tailor the immune response to the corresponding pathogen. To allow for an educated selection, we assessed the effect of different adjuvants on human monocyte-derived dendritic cells (DCs) and their ability to polarize innate and adaptive immune responses. In contrast to commonly used adjuvants, such as aluminum hydroxide, Toll-like receptor (TLR) agonists induced robust phenotypic and functional DC maturation. In a DC-lymphocyte coculture system, we investigated the ensuing immune reactions. While monophosphoryl lipid A synthetic, a TLR4 ligand, induced checkpoint inhibitors indicative for immune exhaustion, the TLR7/8 agonist Resiquimod (R848) induced prominent type-1 interferon and interleukin 6 responses and robust CTL, B-cell, and NK-cell proliferation, which is particularly suited for antiviral immune responses. The recently licensed COVID-19 vaccines, BNT162b and mRNA-1273, are both based on single-stranded RNA. Indeed, we could confirm that the cytokine profile induced by lipid-complexed RNA was almost identical to the pattern induced by R848. Although this awaits further investigation, our results suggest that their efficacy involves the highly efficient antiviral response pattern stimulated by the RNAs’ TLR7/8 activation.

Toll-like receptors: function and roles in lung disease

2004 ◽  
Vol 286 (5) ◽  
pp. L887-L892 ◽  
Author(s):  
Subhendu Basu ◽  
Matthew J. Fenton
Keyword(s):  
Immune Responses ◽  
Allergic Asthma ◽  
Lung Diseases ◽  
Protective Role ◽  
Airway Hyperreactivity ◽  
Toll Like Receptor ◽  
Adaptive Immune ◽  
Bacterial Lipopolysaccharides ◽  
Molecular Patterns

Toll-like receptor (TLR) proteins have been shown to play a pivotal role in both innate and adaptive immune responses in higher vertebrates. TLR proteins enable the host to recognize a large number of pathogen-associated molecular patterns such as bacterial lipopolysaccharides, viral RNA, CpG-containing DNA, and flagellin, among others. Engagement of TLR proteins leads to the upregulation of costimulatory molecules and proinflammatory cytokines, as well as reactive nitrogen and oxygen products. The role of TLR proteins in lung-associated pathologies such as airway hyperreactivity, allergic asthma, and tuberculosis is being intensively studied. This review summarizes many of the findings made to date on the roles of TLR proteins in a variety of lung diseases. Generally, TLR proteins serve a protective role in infectious diseases, such as tuberculosis. The progression of chronic inflammatory lung diseases, such as allergic asthma, can also be influenced by TLR-dependent responses.

scholarly journals Astragalus Polysaccharides Enhance the Immune Response to OVA Antigen in BALB/c Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Yumei Zhou ◽  
Yuhan Zong ◽  
Zihao Liu ◽  
Haihong Zhao ◽  
Xiaoshan Zhao ◽  
...  
Keyword(s):  
Immune Response ◽  
Infectious Diseases ◽  
Immune Responses ◽  
Vaccine Development ◽  
Positive Control ◽  
The Other ◽  
The Past ◽  
Cpg Oligodeoxynucleotide ◽  
Human Use ◽  
Selection Of

Vaccination has been identified as one of the most effective ways to prevent the transmission of infectious diseases in humans and animals. One of the most critical steps in vaccine development is the selection of a suitable adjuvant. Although various adjuvant candidates have been evaluated in the past few decades, only a limited amount of them are nontoxic and safe for human use. Astragalus polysaccharide (APS), due to its lack of toxicity, has been used as an immunomodulator to enhance immune responses. On the other hand, the immune effects of APS on ovalbumin are yet to be examined. Thus, in this study, we analyzed APS’s effects on the immune response to ovalbumin in BALB/c mice. We have also used the classic adjuvant CpG oligodeoxynucleotide as the positive control.

Vitamin A: dietologist’s position

2020 ◽  
pp. 49-57
Author(s):  
S. V. Orlova ◽  
E. A. Nikitina ◽  
L. I. Karushina ◽  
Yu. A. Pigaryova ◽  
O. E. Pronina
Keyword(s):  
Immune Response ◽  
Urinary Tract ◽  
Gastrointestinal Tract ◽  
Vitamin A ◽  
Developed Countries ◽  
Therapeutic Practice ◽  
The Past ◽  
Increased Risk ◽  
Mucous Membranes

Vitamin A (retinol) is one of the key elements for regulating the immune response and controls the division and differentiation of epithelial cells of the mucous membranes of the bronchopulmonary system, gastrointestinal tract, urinary tract, eyes, etc. Its significance in the context of the COVID‑19 pandemic is difficult to overestimate. However, a number of studies conducted in the past have associated the additional intake of vitamin A with an increased risk of developing cancer, as a result of which vitamin A was practically excluded from therapeutic practice in developed countries. Our review highlights the role of vitamin A in maintaining human health and the latest data on its effect on the development mechanisms of somatic pathology.

Is Immune Response Relevant in Interstitial Lung Disease?

2020 ◽  
Vol 16 (1) ◽  
pp. 18-27
Author(s):  
Manzoor M. Khan
Keyword(s):  
Immune Response ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Lung Fibrosis ◽  
Lymphocytic Infiltration ◽  
Therapeutic Strategies ◽  
Mediators Of Inflammation ◽  
Acquired Immune Responses ◽  
Novel Therapeutic Strategies

Interstitial lung disease, a term for a group of disorders, causes lung fibrosis, is mostly refractory to treatments and has a high death rate. After diagnosis the survival is up to 3 years but in some cases the patients live much longer. It involves a heterogenous group of lung diseases that exhibit progressive and irreversible destruction of the lung due to the formation of scars. This results in lung malfunction, disruption of gas exchange, and eventual death because of respiratory failure. The etiology of lung fibrosis is mostly unknown with a few exceptions. The major characteristics of the disease are comprised of injury of epithelial type II cells, increased apoptosis, chronic inflammation, monocytic and lymphocytic infiltration, accumulation of myofibroblasts, and inability to repair damaged tissue properly. These events result in abnormal collagen deposition and scarring. The inflammation process is mild, and the disease is primarily fibrotic driven. Immunosuppressants do not treat the disease but the evidence is evolving that both innate and acquired immune responses a well as the cytokines contribute to at least early progression of the disease. Furthermore, mediators of inflammation including cytokines are involved throughout the process of lung fibrosis. The diverse clinical outcome of the disease is due to different pattern of inflammatory markers. Nonetheless, the development of novel therapeutic strategies requires better understanding of the role of the immune response. This review highlights the role of the immune response in interstitial lung disease and considers the therapeutic strategies based on these observations. For this review several literature data sources were used to assess the role of the immune response in interstitial lung disease and to evaluate the possible therapeutic strategies for the disease.

scholarly journals MicroRNAs: Biological Regulators in Pathogen–Host Interactions

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 113 ◽  
Author(s):  
Stephanie Maia Acuña ◽  
Lucile Maria Floeter-Winter ◽  
Sandra Marcia Muxel
Keyword(s):  
Immune Response ◽  
Infectious Diseases ◽  
Small Rnas ◽  
Immune Cell ◽  
Fine Tuning ◽  
Biological Processes ◽  
Host Interactions ◽  
The Past ◽  
Biological Aspects

An inflammatory response is essential for combating invading pathogens. Several effector components, as well as immune cell populations, are involved in mounting an immune response, thereby destroying pathogenic organisms such as bacteria, fungi, viruses, and parasites. In the past decade, microRNAs (miRNAs), a group of noncoding small RNAs, have emerged as functionally significant regulatory molecules with the significant capability of fine-tuning biological processes. The important role of miRNAs in inflammation and immune responses is highlighted by studies in which the regulation of miRNAs in the host was shown to be related to infectious diseases and associated with the eradication or susceptibility of the infection. Here, we review the biological aspects of microRNAs, focusing on their roles as regulators of gene expression during pathogen–host interactions and their implications in the immune response against Leishmania, Trypanosoma, Toxoplasma, and Plasmodium infectious diseases.

scholarly journals The Role of Macrophages in the Host’s Defense against Sporothrix schenckii

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 905
Author(s):  
Estela Ruiz-Baca ◽  
Armando Pérez-Torres ◽  
Yolanda Romo-Lozano ◽  
Daniel Cervantes-García ◽  
Carlos A. Alba-Fierro ◽  
...  
Keyword(s):  
Immune Responses ◽  
Macrophage Polarization ◽  
Sporothrix Schenckii ◽  
Macrophage Cell ◽  
Cell Recruitment ◽  
Host Pathogen Interaction ◽  
Interaction Processes ◽  
Host Pathogen ◽  
Molecular Patterns

The role of immune cells associated with sporotrichosis caused by Sporothrix schenckii is not yet fully clarified. Macrophages through pattern recognition receptors (PRRs) can recognize pathogen-associated molecular patterns (PAMPs) of Sporothrix, engulf it, activate respiratory burst, and secrete pro-inflammatory or anti-inflammatory biological mediators to control infection. It is important to consider that the characteristics associated with S. schenckii and/or the host may influence macrophage polarization (M1/M2), cell recruitment, and the type of immune response (1, 2, and 17). Currently, with the use of new monocyte-macrophage cell lines, it is possible to evaluate different host–pathogen interaction processes, which allows for the proposal of new mechanisms in human sporotrichosis. Therefore, in order to contribute to the understanding of these host–pathogen interactions, the aim of this review is to summarize and discuss the immune responses induced by macrophage-S. schenckii interactions, as well as the PRRs and PAMPs involved during the recognition of S. schenckii that favor the immune evasion by the fungus.

scholarly journals Essential role of IRAK-4 protein and its kinase activity in Toll-like receptor–mediated immune responses but not in TCR signaling

2007 ◽  
Vol 204 (5) ◽  
pp. 1013-1024 ◽  
Author(s):  
Tatsukata Kawagoe ◽  
Shintaro Sato ◽  
Andreas Jung ◽  
Masahiro Yamamoto ◽  
Kosuke Matsui ◽  
...  
Keyword(s):  
Immune Responses ◽  
Kinase Activity ◽  
Interleukin 1 ◽  
Cell Receptor ◽  
Nuclear Factor Κb ◽  
Toll Like Receptor ◽  
Tcr Signaling ◽  
Mitogen Activated Protein

Interleukin-1 receptor–associated kinase 4 (IRAK-4) was reported to be essential for the Toll-like receptor (TLR)– and T cell receptor (TCR)–mediated signaling leading to the activation of nuclear factor κB (NF-κB). However, the importance of kinase activity of IRAK family members is unclear. In this study, we investigated the functional role of IRAK-4 activity in vivo by generating mice carrying a knockin mutation (KK213AA) that abrogates its kinase activity. IRAK-4KN/KN mice were highly resistant to TLR-induced shock response. The cytokine production in response to TLR ligands was severely impaired in IRAK-4KN/KN as well as IRAK-4−/− macrophages. The IRAK-4 activity was essential for the activation of signaling pathways leading to mitogen-activated protein kinases. TLR-induced IRAK-4/IRAK-1–dependent and –independent pathways were involved in early induction of NF-κB–regulated genes in response to TLR ligands such as tumor necrosis factor α and IκBζ. In contrast to a previous paper (Suzuki, N., S. Suzuki, D.G. Millar, M. Unno, H. Hara, T. Calzascia, S. Yamasaki, T. Yokosuka, N.J. Chen, A.R. Elford, et al. 2006. Science. 311:1927–1932), the TCR signaling was not impaired in IRAK-4−/− and IRAK-4KN/KN mice. Thus, the kinase activity of IRAK-4 is essential for the regulation of TLR-mediated innate immune responses.

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