MGL1 Receptor Plays a Key Role in the Control of <i>T. cruzi</i> Infection by Increasing Macrophage Activation through Modulation of ERK1/2, c-Jun, NF-κB and NLRP3 Pathways
Macrophage galactose-C type lectin (MGL)1 receptor is involved in the recognition of <i>Trypanosoma cruzi</i> (<i>T. cruzi</i>) parasites and is important for the modulation of the innate and adaptive immune responses. However, the mechanism by which MGL1 promotes resistance...
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MDPI AG
2020-01-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/1/108 |
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| author | Tonathiu Rodriguez Thalia Pacheco-Fernández Alicia Vázquez-Mendoza Oscar Nieto-Yañez Imelda Juárez-Avelar José L. Reyes Luis I. Terrazas Miriam Rodriguez-Sosa |
| author_facet | Tonathiu Rodriguez Thalia Pacheco-Fernández Alicia Vázquez-Mendoza Oscar Nieto-Yañez Imelda Juárez-Avelar José L. Reyes Luis I. Terrazas Miriam Rodriguez-Sosa |
| author_sort | Tonathiu Rodriguez |
| collection | DOAJ |
| description | Macrophage galactose-C type lectin (MGL)1 receptor is involved in the recognition of <i>Trypanosoma cruzi</i> (<i>T. cruzi</i>) parasites and is important for the modulation of the innate and adaptive immune responses. However, the mechanism by which MGL1 promotes resistance to <i>T. cruzi</i> remains unclear. Here, we show that MGL1 knockout macrophages (MGL1<sup>−/−</sup> Mφ) infected in vitro with <i>T. cruzi</i> were heavily parasitized and showed decreased levels of reactive oxygen species (ROS), nitric oxide (NO), IL-12 and TNF-α compared to wild-type macrophages (WT Mφ). MGL1<sup>−/−</sup> Mφ stimulated in vitro with <i>T. cruzi</i> antigen (<i>Tc</i>Ag) showed low expression of TLR-2, TLR-4 and MHC-II, which resulted in deficient splenic cell activation compared with similar co-cultured WT Mφ. Importantly, the activation of p-ERK1/2, p-c-Jun and p-NF-κB p65 were significantly reduced in MGL1<sup>−/−</sup> Mφ exposed to <i>Tc</i>Ag. Similarly, procaspase 1, caspase 1 and NLRP3 inflammasome also displayed a reduced expression that was associated with low IL-β production. Our data reveal a previously unappreciated role for MGL1 in Mφ activation through the modulation of ERK1/2, c-Jun, NF-κB and NLRP3 signaling pathways, and to the development of protective innate immunity against experimental <i>T. cruzi</i> infection. |
| first_indexed | 2024-03-12T07:20:27Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T07:20:27Z |
| publishDate | 2020-01-01 |
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| series | Cells |
| spelling | doaj.art-aa1f245e1a9e4e42b1264244c11decd42023-09-02T22:28:44ZengMDPI AGCells2073-44092020-01-019110810.3390/cells9010108cells9010108MGL1 Receptor Plays a Key Role in the Control of <i>T. cruzi</i> Infection by Increasing Macrophage Activation through Modulation of ERK1/2, c-Jun, NF-κB and NLRP3 PathwaysTonathiu Rodriguez0Thalia Pacheco-Fernández1Alicia Vázquez-Mendoza2Oscar Nieto-Yañez3Imelda Juárez-Avelar4José L. Reyes5Luis I. Terrazas6Miriam Rodriguez-Sosa7Unidad de Biomedicina (UBIMED), Facultad de Estudios Superiores Iztacala (FES-Iztacala), Universidad Nacional Autónoma de México (UNAM). Tlalnepantla, Estado de México 54090, MexicoUnidad de Biomedicina (UBIMED), Facultad de Estudios Superiores Iztacala (FES-Iztacala), Universidad Nacional Autónoma de México (UNAM). Tlalnepantla, Estado de México 54090, MexicoCarrera de Optometría, FES-Iztacala, UNAM. Tlalnepantla, Estado de México 54090, MexicoUnidad de Biomedicina (UBIMED), Facultad de Estudios Superiores Iztacala (FES-Iztacala), Universidad Nacional Autónoma de México (UNAM). Tlalnepantla, Estado de México 54090, MexicoUnidad de Biomedicina (UBIMED), Facultad de Estudios Superiores Iztacala (FES-Iztacala), Universidad Nacional Autónoma de México (UNAM). Tlalnepantla, Estado de México 54090, MexicoUnidad de Biomedicina (UBIMED), Facultad de Estudios Superiores Iztacala (FES-Iztacala), Universidad Nacional Autónoma de México (UNAM). Tlalnepantla, Estado de México 54090, MexicoUnidad de Biomedicina (UBIMED), Facultad de Estudios Superiores Iztacala (FES-Iztacala), Universidad Nacional Autónoma de México (UNAM). Tlalnepantla, Estado de México 54090, MexicoUnidad de Biomedicina (UBIMED), Facultad de Estudios Superiores Iztacala (FES-Iztacala), Universidad Nacional Autónoma de México (UNAM). Tlalnepantla, Estado de México 54090, MexicoMacrophage galactose-C type lectin (MGL)1 receptor is involved in the recognition of <i>Trypanosoma cruzi</i> (<i>T. cruzi</i>) parasites and is important for the modulation of the innate and adaptive immune responses. However, the mechanism by which MGL1 promotes resistance to <i>T. cruzi</i> remains unclear. Here, we show that MGL1 knockout macrophages (MGL1<sup>−/−</sup> Mφ) infected in vitro with <i>T. cruzi</i> were heavily parasitized and showed decreased levels of reactive oxygen species (ROS), nitric oxide (NO), IL-12 and TNF-α compared to wild-type macrophages (WT Mφ). MGL1<sup>−/−</sup> Mφ stimulated in vitro with <i>T. cruzi</i> antigen (<i>Tc</i>Ag) showed low expression of TLR-2, TLR-4 and MHC-II, which resulted in deficient splenic cell activation compared with similar co-cultured WT Mφ. Importantly, the activation of p-ERK1/2, p-c-Jun and p-NF-κB p65 were significantly reduced in MGL1<sup>−/−</sup> Mφ exposed to <i>Tc</i>Ag. Similarly, procaspase 1, caspase 1 and NLRP3 inflammasome also displayed a reduced expression that was associated with low IL-β production. Our data reveal a previously unappreciated role for MGL1 in Mφ activation through the modulation of ERK1/2, c-Jun, NF-κB and NLRP3 signaling pathways, and to the development of protective innate immunity against experimental <i>T. cruzi</i> infection.https://www.mdpi.com/2073-4409/9/1/108c-type lectin-like receptorsmacrophage galactose-c type lectinmouse mgl<i>trypanosoma cruzi</i>prrsinnate immunity response |
| spellingShingle | Tonathiu Rodriguez Thalia Pacheco-Fernández Alicia Vázquez-Mendoza Oscar Nieto-Yañez Imelda Juárez-Avelar José L. Reyes Luis I. Terrazas Miriam Rodriguez-Sosa MGL1 Receptor Plays a Key Role in the Control of <i>T. cruzi</i> Infection by Increasing Macrophage Activation through Modulation of ERK1/2, c-Jun, NF-κB and NLRP3 Pathways Cells c-type lectin-like receptors macrophage galactose-c type lectin mouse mgl <i>trypanosoma cruzi</i> prrs innate immunity response |
| title | MGL1 Receptor Plays a Key Role in the Control of <i>T. cruzi</i> Infection by Increasing Macrophage Activation through Modulation of ERK1/2, c-Jun, NF-κB and NLRP3 Pathways |
| title_full | MGL1 Receptor Plays a Key Role in the Control of <i>T. cruzi</i> Infection by Increasing Macrophage Activation through Modulation of ERK1/2, c-Jun, NF-κB and NLRP3 Pathways |
| title_fullStr | MGL1 Receptor Plays a Key Role in the Control of <i>T. cruzi</i> Infection by Increasing Macrophage Activation through Modulation of ERK1/2, c-Jun, NF-κB and NLRP3 Pathways |
| title_full_unstemmed | MGL1 Receptor Plays a Key Role in the Control of <i>T. cruzi</i> Infection by Increasing Macrophage Activation through Modulation of ERK1/2, c-Jun, NF-κB and NLRP3 Pathways |
| title_short | MGL1 Receptor Plays a Key Role in the Control of <i>T. cruzi</i> Infection by Increasing Macrophage Activation through Modulation of ERK1/2, c-Jun, NF-κB and NLRP3 Pathways |
| title_sort | mgl1 receptor plays a key role in the control of i t cruzi i infection by increasing macrophage activation through modulation of erk1 2 c jun nf κb and nlrp3 pathways |
| topic | c-type lectin-like receptors macrophage galactose-c type lectin mouse mgl <i>trypanosoma cruzi</i> prrs innate immunity response |
| url | https://www.mdpi.com/2073-4409/9/1/108 |
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