Nonbilayer Phospholipid Arrangements Are Toll-Like Receptor-2/6 and TLR-4 Agonists and Trigger Inflammation in a Mouse Model Resembling Human Lupus

Wong-Baeza, Carlos; Tescucano, Alonso; Astudillo, Horacio; Reséndiz, Albany; Landa, Carla; España, Luis Pérez; Serafín‐López, Jeanet; Estrada-Garcı́a, Iris; Estrada‐Parra, Sergio; Flores‐Romo, Leopoldo; Wong, Carlos; Baeza, Isabel

doi:10.1155/2015/369462

Cited by 9 publications

(28 citation statements)

References 37 publications

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“…These iNKT cells can be found in germinal centers and they provide help to B cells in a CD40–CD40L-dependent manner, which leads to the production of IgG antibodies ( 33 , 36 , 37 ). It is, thus, conceivable that iNKT cells might be cooperating with B cells for the production of anti-NPA IgG antibodies ( 38 ), but this needs to be demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus

Wong-Baeza

Reséndiz-Mora²,

Donis-Maturano

et al. 2016

Front. Immunol.

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Anti-lipid IgG antibodies are produced in some mycobacterial infections and in certain autoimmune diseases [such as anti-phospholipid syndrome, systemic lupus erythematosus (SLE)]. However, few studies have addressed the B cell responses underlying the production of these immunoglobulins. Anti-lipid IgG antibodies are consistently found in a murine model resembling human lupus induced by chlorpromazine-stabilized non-bilayer phospholipid arrangements (NPA). NPA are transitory lipid associations found in the membranes of most cells; when NPA are stabilized they can become immunogenic and induce specific IgG antibodies, which appear to be involved in the development of the mouse model of lupus. Of note, anti-NPA antibodies are also detected in patients with SLE and leprosy. We used this model of lupus to investigate in vivo the cellular mechanisms that lead to the production of anti-lipid, class-switched IgG antibodies. In this murine lupus model, we found plasma cells (Gr1−, CD19−, CD138+) producing NPA-specific IgGs in the draining lymph nodes, the spleen, and the bone marrow. We also found a significant number of germinal center B cells (IgD−, CD19+, PNA+) specific for NPA in the draining lymph nodes and the spleen, and we identified in situ the presence of NPA in these germinal centers. By contrast, very few NPA-specific, extrafollicular reaction B cells (B220+, Blimp1+) were found. Moreover, when assessing the anti-NPA IgG antibodies produced during the experimental protocol, we found that the affinity of these antibodies progressively increased over time. Altogether, our data indicate that, in this murine model resembling human lupus, B cells produce anti-NPA IgG antibodies mainly via germinal centers.

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Section: Discussionmentioning

confidence: 99%

Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus

Wong-Baeza

Reséndiz-Mora²,

Donis-Maturano

et al. 2016

Front. Immunol.

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“…In previous studies, we described the development of the mouse model of autoimmune disease resembling human lupus [ 4 , 5 , 7 ]. Sixteen female BALB/c mice were obtained from the Laboratory Animal Production and Testing Unit at CINVESTAV-IPN and were housed in the animal facility at our institution.…”

Section: Methodsmentioning

confidence: 99%

“…The signaling network summarizing our current and previous results was developed using Cytoscape v3.4.0 [ 18 ] to assess interactions between the mRNA results found in TLR4 signaling pathways [ 7 ] and the known targets for miR-155-5p, miR-200a-3p, miR-21a-5p, and miR-146b-5p, trying to find the role of those miRNAs on the development of murine lupus-like disease. These four miRNAs were chosen among the six detected as important in the lupus-like model by miRNA arrays, together with miR-342-3p [ 14 , 15 ], because they were the only found in the compendium database of experimentally determined miRNA target genes created by the Cancer miRNA Regulatory Network [ 19 ].…”

Section: Methodsmentioning

confidence: 99%

“…Using this compendium database, a network was developed to distinguish common targets for these four miRNAs, which were further analyzed with Cytoscape and its associated databases to find relationships among the four miRNAs and their targets, allowing us to highlight only two of the original four miRNAs selected. Afterwards, the final signaling network was specifically compared with TLR4 signaling pathways reported in WikiPathways [ 20 ] and recent literature [ 21 – 23 ] to find key players associated with the role of these two miRNAs and our previous data on TLR4 signaling [ 7 ].…”

Section: Methodsmentioning

confidence: 99%

“…Liposomes with NPA also induce TLR-4/MD-2 signaling and, to a lower extent, TLR-2/TLR-6 signaling, both in TLR-expressing HEK cells and bone marrow-derived macrophages (from BALB/c mice) [ 7 ]. Mice with lupus-like disease had shown an increase in serum concentrations of proinflammatory cytokines, a higher number of TLR-expressing spleen cells, and an augmented gene expression associated with TICAM1- (TRIF-) dependent TLR-4 signaling (including IFNA1 and IFNA2 ) and complement activation.…”

Section: Introductionmentioning

confidence: 99%

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Dysregulation of miR-155-5p and miR-200-3p and the Anti-Non-Bilayer Phospholipid Arrangement Antibodies Favor the Development of Lupus in Three Novel Murine Lupus Models

Zárate-Neira

Sánchez-Barbosa

Pedroza-Torres

et al. 2017

Journal of Immunology Research

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Systemic lupus erythematosus (SLE) is characterized by deregulated activation of T and B cells, autoantibody production, and consequent formation of immune complexes. Liposomes with nonbilayer phospholipid arrangements (NPA), induced by chlorpromazine, procainamide, or manganese, provoke a disease resembling human lupus when administered to mice. These mice produce anti-NPA IgM and IgG antibodies and exhibit an increased number of TLR-expressing spleen cells and a modified gene expression associated with TICAM1-dependent TLR-4 signaling (including IFNA1 and IFNA2) and complement activation. Additionally, they showed a diminished gene expression related to apoptosis and NK cell activation. We hypothesized that such gene expression may be affected by miRNAs and so miRNA expression was studied. Twelve deregulated miRNAs were found. Six of them were common to the three lupus-like models. Their validation by qRT-PCR and TaqMan probes, including miR-342-3p, revealed that miR-155-5p and miR-200a-3p expression was statistically significant. Currently described functions for these miRNAs in autoimmune diseases such as SLE reveal their participation in inflammation, interferon production, germinal center responses, and antibody maturation. Taking into account these findings, we propose miR-155-5p and miR-200a-3p, together with the anti-NPA antibodies, as key players in the murine lupus-like models and possible biomarkers of the human SLE.

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Extracellular vesicles fromMycobacterium tuberculosis–infected neutrophils induce maturation of monocyte-derived dendritic cells and activation of antigen-specific Th1 cells

Vázquez-Flores

Castañeda-Casimiro

Vallejo-Castillo

et al. 2023

Journal of Leukocyte Biology

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Tuberculosis remains one of the leading public health problems in the world. The mechanisms that lead to the activation of the immune response against Mycobacterium tuberculosis (Mtb) have been extensively studied, with a focus on the role of cytokines as the main signals for immune cell communication. However, less is known about the role of other signals, such as extracellular vesicles (EVs), in the communication between immune cells, particularly during the activation of the adaptive immune response. In this study, we determined that EVs released by human neutrophils infected with Mtb (EV-Mtb) contained several host proteins that are ectosome markers. In addition, we demonstrated that EV-Mtb released after only 30 min of infection carried mycobacterial antigens and pathogen-associated molecular patterns, and we identified 15 mycobacterial proteins that were consistently found in high concentrations in EV-Mtb; these proteins contain epitopes for CD4 T cell activation. We found that EV-Mtb increased the expression of the co-stimulatory molecule CD80 and of the co-inhibitory molecule PD-L1 on immature monocyte-derived dendritic cells. We also found that immature and mature dendritic cells treated with EV-Mtb were able to induce IFN-γ production by autologous Mtb antigen-specific CD4 T cells, indicating that these EVs acted as antigen carriers and transferred mycobacterial proteins to the antigen-presenting cells. Our results provide evidence that EV-Mtb participate in the activation of the adaptive immune response against Mtb.

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Nonbilayer Phospholipid Arrangements Are Toll-Like Receptor-2/6 and TLR-4 Agonists and Trigger Inflammation in a Mouse Model Resembling Human Lupus

Cited by 9 publications

References 37 publications

Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus

Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus

Dysregulation of miR-155-5p and miR-200-3p and the Anti-Non-Bilayer Phospholipid Arrangement Antibodies Favor the Development of Lupus in Three Novel Murine Lupus Models

Extracellular vesicles fromMycobacterium tuberculosis–infected neutrophils induce maturation of monocyte-derived dendritic cells and activation of antigen-specific Th1 cells

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