MGL1 Receptor Plays a Key Role in the Control of T. cruzi Infection by Increasing Macrophage Activation through Modulation of ERK1/2, c-Jun, NF-κB and NLRP3 Pathways

Rodríguez, Tonathiu; Pacheco-Fernández, Thalia; Vázquez-Mendoza, Alicia; Nieto-Yañez, Oscar; Juárez-Avelar, Imelda; Reyes, José L.; Terrazas, Luis I.; Rodrı́guez-Sosa, Miriam

doi:10.3390/cells9010108

Cited by 12 publications

(15 citation statements)

References 56 publications

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“…As such, parasites have evolved numerous strategies to either up- or down-regulate NF-κB. These include, but are not limited to, direct phosphorylation of NF-κB pathway proteins or their inhibitors [ 91 ], binding of certain receptors to activate specific pathways [ 56 , 57 , 61 ], or cleavage of NF-κB proteins via parasite proteases [ 62 , 98 , 111 ]. While each modulates NF-κB activity, the resulting outcomes of these actions are dependent on the cell types involved and whether NF-κB activity is increased or decreased.…”

Section: Discussionmentioning

confidence: 99%

“…Other receptors that recognize T. cruzi and are involved in subsequent activation of NF-κB have been identified; macrophage galactose-C type lectin (MGL1) receptor is critical for the optimal activation of macrophages during T. cruzi infection. MGL1 is proposed to recognize soluble T. cruzi Lysate Antigen (TcAg) [ 61 ]. A trypanosome antigen that can disrupt the protective host response via modulation of NF-κB is cruzain from T. cruzi .…”

Section: Trypanosoma Sppmentioning

confidence: 99%

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The Role of Nuclear Factor Kappa B (NF-κB) in the Immune Response against Parasites

Bąska

Norbury

2022

Pathogens

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The immune system consists of various cells, organs, and processes that interact in a sophisticated manner to defend against pathogens. Upon initial exposure to an invader, nonspecific mechanisms are raised through the activation of macrophages, monocytes, basophils, mast cells, eosinophils, innate lymphoid cells, or natural killer cells. During the course of an infection, more specific responses develop (adaptive immune responses) whose hallmarks include the expansion of B and T cells that specifically recognize foreign antigens. Cell to cell communication takes place through physical interactions as well as through the release of mediators (cytokines, chemokines) that modify cell activity and control and regulate the immune response. One regulator of cell states is the transcription factor Nuclear Factor kappa B (NF-κB) which mediates responses to various stimuli and is involved in a variety of processes (cell cycle, development, apoptosis, carcinogenesis, innate and adaptive immune responses). It consists of two protein classes with NF-κB1 (p105/50) and NF-κB2 (p100/52) belonging to class I, and RelA (p65), RelB and c-Rel belonging to class II. The active transcription factor consists of a dimer, usually comprised of both class I and class II proteins conjugated to Inhibitor of κB (IκB). Through various stimuli, IκB is phosphorylated and detached, allowing dimer migration to the nucleus and binding of DNA. NF-κB is crucial in regulating the immune response and maintaining a balance between suppression, effective response, and immunopathologies. Parasites are a diverse group of organisms comprised of three major groups: protozoa, helminths, and ectoparasites. Each group induces distinct effector immune mechanisms and is susceptible to different types of immune responses (Th1, Th2, Th17). This review describes the role of NF-κB and its activity during parasite infections and its contribution to inducing protective responses or immunopathologies.

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Section: Discussionmentioning

confidence: 99%

Section: Trypanosoma Sppmentioning

confidence: 99%

The Role of Nuclear Factor Kappa B (NF-κB) in the Immune Response against Parasites

Bąska

Norbury

2022

Pathogens

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“…These interactions lead to Th2 lineage via IL-4 production [ 38 ]. Mouse MGL-1 can recognize N -GalNAc and galactose [ 39 ]. Interestingly, Pneumocystis has indeed been shown to contain GalNAc residues [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Additional C-type lectin receptors mediate interactions with Pneumocystis organisms and major surface glycoprotein

Kottom

Carmona

Schaefbauer

et al. 2021

Journal of Medical Microbiology

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Introduction. Pathogen-associated molecular patterns’ (PAMPs) are microbial signatures that are recognized by host myeloid C-type lectin receptors (CLRs). These CLRs interact with micro-organisms via their carbohydrate recognition domains (CRDs) and engage signalling pathways within the cell resulting in pro-inflammatory and microbicidal responses. Gap statement. In this article, we extend our laboratory study of additional CLRs that recognize fungal ligands against Pneumocystis murina and Pneumocystis carinii and their purified major surface glycoproteins (Msgs). Aim. To study the potential of newly synthesized hFc-CLR fusions on binding to Pneumocystis and its Msg. Methods. A library of new synthesized hFc-CLR fusions was screened against Pneumocystis murina and Pneumocystis carinii organisms and their purified major surface glycoproteins (Msgs) found on the respective fungi via modified ELISA. Immunofluorescence assay (IFA) was implemented and quantified to verify results. mRNA expression analysis by quantitative PCR (q-PCR) was employed to detect respective CLRs found to bind fungal organisms in the ELISA and determine their expression levels in the mouse immunosuppressed Pneumocystis pneumonia (PCP) model. Results. We detected a number of the CLR hFc-fusions displayed significant binding with P. murina and P. carinii organisms, and similarly to their respective Msgs. Significant organism and Msg binding was observed for CLR members C-type lectin domain family 12 member A (CLEC12A), Langerin, macrophage galactose-type lectin-1 (MGL-1), and specific intracellular adhesion molecule-3 grabbing non-integrin homologue-related 3 (SIGNR3). Immunofluorescence assay (IFA) with the respective CLR hFc-fusions against whole P. murina life forms corroborated these findings. Lastly, we surveyed the mRNA expression profiles of the respective CLRs tested above in the mouse immunosuppressed Pneumocystis pneumonia (PCP) model and determined that macrophage galactose type C-type lectin (Mgl-1), implicated in recognizing terminal N-acetylgalactosamine (GalNAc) found in the glycoproteins of microbial pathogens was significantly up-regulated during infection. Conclusion. The data herein add to the growing list of CLRs recognizing Pneumocystis and provide insights for further study of organism/host immune cell interactions.

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“…is study followed the same procedures and guidelines to ensure the well-being of the experimental subjects of Rodriguez et al, and the description of the methods partly reproduces their wording [12].…”

Section: Experimental Animalsmentioning

confidence: 99%

Anti-Diabetic Effects of Cucurbitacins from Ibervillea lindheimeri on Induced Mouse Diabetes

Navia

Figueroa-Hernández

Rodríguez‐Zavala

et al. 2022

Journal of Chemistry

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Mexico has a great tradition of using medicinal plants against diabetes. For example, species from the genus Ibervillea traditionally known as “wereque” in Mexican popular medicine have a long ethnobotanical history as anti-diabetic agents. Previous studies by our group indicated that ethyl acetate extract from Ibervillea lindheimeri (I. lindheimeri) roots reduced glucose in mice with chemically induced diabetes. In this work, the primary metabolites of the ethyl acetate extract of I. lindheimeri; 23,24-dihydrocucurbitacin D (1); 2-O-β glucopyranosyl-23,24-dihydrocucurbitacin D (2), and acetylated compounds (3) and (4) obtained from 1 and 2, respectively, were evaluated as anti-hyperglycemic agents in a murine model of chemically induced diabetes. Our results showed that cucurbitacins 1, 2, and 4 reduced glycemia in diabetic CD1 mice compared to the control diabetic group. In addition, the results suggest that compounds 1, 2, and 4 promote glucose transporter type 4 (Glut4) translocation to the plasma membrane (PM) mainly in epididymal adipose tissue (EAT), AMP-activated protein kinase (AMPK) activation in soleus muscle (SM) or dual activation of AMPK, and protein kinase B (AKT) in EAT in an insulin-independent manner when compared to controls. All results together indicate that the isolated cucurbitacins are responsible for the anti-diabetic properties of I. lindheimeri acting predominantly on adipose tissue and call attention to this species as a new source of anti-diabetic compounds.

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MGL1 Receptor Plays a Key Role in the Control of T. cruzi Infection by Increasing Macrophage Activation through Modulation of ERK1/2, c-Jun, NF-κB and NLRP3 Pathways

Cited by 12 publications

References 56 publications

The Role of Nuclear Factor Kappa B (NF-κB) in the Immune Response against Parasites

The Role of Nuclear Factor Kappa B (NF-κB) in the Immune Response against Parasites

Additional C-type lectin receptors mediate interactions with Pneumocystis organisms and major surface glycoprotein

Anti-Diabetic Effects of Cucurbitacins from Ibervillea lindheimeri on Induced Mouse Diabetes

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