Brucella abortus induces mast cell activation through TLR-2 and TLR-4

Domínguez-Flores, Adriana; López, Gloria M. Rodríguez; Soria-Castro, Rodolfo; López‐Santiago, Rubén; Rodríguez‐Cortés, Octavio; Pérez‐Tapia, Sonia Mayra; Chávez‐Blanco, Alma; Estrada‐Parra, Sergio; Flores-Mejía, Raúl; Chacón‐Salinas, Rommel

doi:10.1016/j.micpath.2023.106005

Cited by 7 publications

(7 citation statements)

References 53 publications

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“…Protein–protein docking has become an important tool in the fields of immunoinformatics and pharmacological research. TLR2 and TLR4 are particularly important because they play a crucial role in generating specific T cells and are essential for the body’s defense against Brucella infection ( 69 , 70 ). Therefore, we selected TLR2 and TLR4 as the receptors for molecular docking with MEV-Fc.…”

Section: Discussionmentioning

confidence: 99%

Design of a multi-epitope vaccine against brucellosis fused to IgG-fc by an immunoinformatics approach

Wu,

Wang,

Ali

et al. 2023

Front. Vet. Sci.

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IntroductionBrucella, a type of intracellular Gram-negative bacterium, has unique features and acts as a zoonotic pathogen. It can lead to abortion and infertility in animals. Eliminating brucellosis becomes very challenging once it spreads among both humans and animals, putting a heavy burden on livestock and people worldwide. Given the increasing spread of brucellosis, it is crucial to develop improved vaccines for susceptible animals to reduce the disease’s impact.MethodsIn this study, we effectively used an immunoinformatics approach with advanced computer software to carefully identify and analyze important antigenic parts of Brucella abortus. Subsequently, we skillfully designed chimeric peptides to enhance the vaccine’s strength and effectiveness. We used computer programs to find four important parts of the Brucella bacteria that our immune system recognizes. Then, we carefully looked for eight parts that are recognized by a type of white blood cell called cytotoxic T cells, six parts recognized by T helper cells, and four parts recognized by B cells. We connected these parts together using a special link, creating a strong new vaccine. To make the vaccine even better, we added some extra parts called molecular adjuvants. These included something called human β-defensins 3 (hBD-3) that we found in a database, and another part that helps the immune system called PADRE. We attached these extra parts to the beginning of the vaccine. In a new and clever way, we made the vaccine even stronger by attaching a part from a mouse’s immune system to the end of it. This created a new kind of vaccine called MEV-Fc. We used advanced computer methods to study how well the MEV-Fc vaccine interacts with certain receptors in the body (TLR-2 and TLR-4).ResultsIn the end, Immunosimulation predictions showed that the MEV-Fc vaccine can make the immune system respond strongly, both in terms of cells and antibodies.DiscussionIn summary, our results provide novel insights for the development of Brucella vaccines. Although further laboratory experiments are required to assess its protective effect.

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Section: Discussionmentioning

confidence: 99%

Design of a multi-epitope vaccine against brucellosis fused to IgG-fc by an immunoinformatics approach

Wu,

Wang,

Ali

et al. 2023

Front. Vet. Sci.

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“…Recently, other authors found similar results with the Brucella abortus bacterium. In this publication, they show that the activation of TLR2 and TLR4 by outer membrane protein and LPS, respectively, induces a cell signaling cascade and the production of IL-6, TNF-α, CCL3, CCL4, and CCL5 ( 96 ).…”

Section: Role Of Mast Cells In Bacterial Infectionsmentioning

confidence: 99%

MASTer cell: chief immune modulator and inductor of antimicrobial immune response

Suárez Vázquez,

López López,

Salinas Carmona

2024

Front. Immunol.

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Mast cells have long been recognized for their involvement in allergic pathology through the immunoglobulin E (IgE)-mediated degranulation mechanism. However, there is growing evidence of other “non-canonical” degranulation mechanisms activated by certain pathogen recognition receptors. Mast cells release several mediators, including histamine, cytokines, chemokines, prostaglandins, and leukotrienes, to initiate and enhance inflammation. The chemical nature of activating stimuli influences receptors, triggering mechanisms for the secretion of formed and new synthesized mediators. Mast cells have more than 30 known surface receptors that activate different pathways for direct and indirect activation by microbes. Different bacterial strains stimulate mast cells through various ligands, initiating the innate immune response, which aids in clearing the bacterial burden. Mast cell interactions with adaptative immune cells also play a crucial role in infections. Recent publications revealed another “non-canonical” degranulation mechanism present in tryptase and chymase mast cells in humans and connective tissue mast cells in mice, occurring through the activation of the Mas-related G protein–coupled receptor (MRGPRX2/b2). This receptor represents a new therapeutic target alongside antibiotic therapy. There is an urgent need to reconsider and redefine the biological role of these MASTer cells of innate immunity, extending beyond their involvement in allergic pathology.

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“…MCs express TLRs in their surface membranes, which allow them to react against microorganisms as a protective immune response. TLR4 or CD48 activation leads to the secretion of TNF by MCs after antigen binding, an important reaction for immune cell activation and lymphocyte recruitment [ 68 ]. Moreover, the secretion of TNF by MCs seems to be crucial for developing and protecting the immune response to bacteria and viruses [ 69 ].…”

Section: Tumor Necrosis Factor (Tnf)mentioning

confidence: 99%

Impact of TNF and IL-33 Cytokines on Mast Cells in Neuroinflammation

Conti,

Ronconi,

Lauritano

et al. 2024

IJMS

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Mast cells (MCs) are derived from hematopoietic progenitors, mature in vascularized tissues, and participate in innate and acquired immunity. Neuroinflammation is a highly debated topic in the biomedical literature; however, the impact of tumor necrosis factor (TNF) and IL-33 on MCs in the brain has not been widely addressed. MCs can be activated by IgE binding to FcεRI, as well as by different antigens. After activation, MCs mediate various immunological and inflammatory responses through TNF and IL-33. TNF has two receptors: TNFR1, a p55 molecule, and TNFR2, a p75 molecule. This cytokine is the only one of its kind to be stored in the granules of MCs and can also be generated by de novo synthesis via mRNA. In the central nervous system (CNS), TNF is produced almost exclusively by microglial cells, neurons, astrocytes, and, minimally, by endothelial cells. After its release into brain tissue, TNF rapidly induces the adhesion molecules endothelial leukocyte adhesion molecule 1 (ELAM-1), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) in endothelial cells. TNF causes the chemoattraction of neutrophils by inducing several molecules, including CXC chemokines (IL-8). Both MCs and microglial cells act as a primary barrier against foreign molecules in the CNS, producing pro-inflammatory cytokines such as IL-33. IL-33 belongs to the IL-1 family, is activated through the ST2L/IL1-RAcP receptor complex, and mediates both the innate and adaptive immune response. IL-33 is a nuclear transcription factor expressed in the brain, where it induces pro-inflammatory cytokines (TNF and IL-1) and chemokines (CCL2, CCL3, CCL5, and CXCL10). Therefore, MCs and microglia in the CNS are a source of pro-inflammatory cytokines, including TNF and IL-33, that mediate many brain diseases. The inhibition of TNF and IL-33 may represent a new therapeutic approach that could complement existing neuroinflammatory therapies.

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Brucella abortus induces mast cell activation through TLR-2 and TLR-4

Cited by 7 publications

References 53 publications

Design of a multi-epitope vaccine against brucellosis fused to IgG-fc by an immunoinformatics approach

Design of a multi-epitope vaccine against brucellosis fused to IgG-fc by an immunoinformatics approach

MASTer cell: chief immune modulator and inductor of antimicrobial immune response

Impact of TNF and IL-33 Cytokines on Mast Cells in Neuroinflammation

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