Cytokine production and signalling in human THP-1 macrophages is dependent on Toxocara canis glycans

Długosz, Ewa; Basałaj, Katarzyna; Zawistowska-Deniziak, Anna

doi:10.1007/s00436-019-06405-8

Cited by 18 publications

(15 citation statements)

References 73 publications

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“…The activation of Mφ by infectious and non-infectious insults is usually triggered by the recognition of the antigen by receptors on the surface of Mφ; this leads to the activation of the NFκ-B and c-Jun transcription factors, which play key roles in modulating the expression of many proinflammatory genes and innate immune response signaling [32][33][34]. Consequently, IL-10, TNF-α, and NO production by Mφ correlates with the strength of NFκ-B activation.…”

Section: Mgl1 Deficiency In Bmmφ Results In Reduced Activation Of Thementioning

confidence: 99%

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

Pacheco-Fernández

Vázquez-Mendoza

et al. 2020

Cells

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Macrophage galactose-C type lectin (MGL)1 receptor is involved in the recognition of Trypanosoma cruzi (T. cruzi) parasites and is important for the modulation of the innate and adaptive immune responses. However, the mechanism by which MGL1 promotes resistance to T. cruzi remains unclear. Here, we show that MGL1 knockout macrophages (MGL1−/− Mφ) infected in vitro with T. cruzi 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−/− Mφ stimulated in vitro with T. cruzi antigen (TcAg) 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−/− Mφ exposed to TcAg. 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 T. cruzi infection.

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Section: Mgl1 Deficiency In Bmmφ Results In Reduced Activation Of Thementioning

confidence: 99%

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

Pacheco-Fernández

Vázquez-Mendoza

et al. 2020

Cells

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“…Finally, we foun that 3D4/2, without LPS stimulation, secreted a small amount of TNF-α. Other studies also report that macrophages can secrete limited cytokines without any treatment, such as in the research of Dlugosz et al [50] and Sharma et al [51]. It is possible that macrophages that secreted cytokines that caused CM in the control group inhibited FA absorption in IPEC-J2.…”

Section: Discussionmentioning

confidence: 95%

LPS Inhibits Fatty Acid Absorption in Enterocytes through TNF-α Secreted by Macrophages

Liu

Kai

et al. 2019

Cells

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Diarrhea, such as steatorrhea, could result from fat absorption disorders, which could be caused by many factors, including Escherichia coli infection. However, it is not clear how E. coli affects fatty acid absorption in animals. Lipopolysaccharide (LPS), as one of the main pathogenic components of E. coli, is the main cause of the virulence of E. coli. Therefore, we used LPS to explore the underlying mechanism of E. coli that causes the inhibition of fatty acid absorption in the intestine. In this study, we found that LPS caused apoptosis of intestinal epithelial cells in mice. Further, caspase-3 activation caused the inhibition of fatty acid absorption in the intestinal porcine enterocyte cell line (IPEC-J2). However, direct treatment of LPS did not induce any significant change in fatty acid absorption in IPEC-J2. We then prepared conditioned medium of LPS-treated porcine macrophage cell line (3D4/2) for incubating IPEC-J2, as LPS initiates inflammation by activating immune cells. The conditioned medium decreased fatty acid absorption and caspase-3 activation in IPEC-J2. While inhibiting the activation of caspase-3 in IPEC-J2, conditioned medium no longer caused serious deficiency of fatty acid absorption. As IL-1β, IL-6, and TNF-α in conditioned medium increase significantly, IPEC-J2 was treated with IL-1β, IL-6, and TNF-α, respectively. Only TNF-α induced caspase-3 activation in IPEC-J2. Reducing the secretion of TNF-α in 3D4/2, there was no obvious activation of caspase-3 in IPEC-J2, and fatty acid absorption recovered effectively. Based on the above results, we hold the opinion that LPS does not suppress fatty acid absorption directly in the intestine, but may work on macrophages that secrete cytokines, such as TNF-α, inducing caspase-3 activation and finally leading to the inhibition of fatty acid absorption in intestine.

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“…To gain first insights whether MGL-1 might play a role in Toxocara -induced APC effector functions, bone marrow-derived dendritic cell (BMDC) stimulation assays were performed. We assessed the Th2-driving cytokine IL-6 and the early pro-inflammatory cytokine tumour necrosis factor (TNF) as these were previously shown to be affected upon Toxocara infection or Toxocara antigen stimulation [ 8 , 10 , 11 , 12 , 23 , 24 , 25 , 26 ]. In general, stimulation of BMDCs with lipopolysaccharide (LPS) resulted in a significant increase of IL-6 and TNF secretion, which was even more pronounced upon TSOM and TES stimulation ( Figure 4 A).…”

Section: Resultsmentioning

confidence: 99%

Toxocara canis and Toxocara cati Somatic and Excretory-Secretory Antigens Are Recognised by C-Type Lectin Receptors

2021

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Toxocara canis and Toxocara cati, the worldwide occurring intestinal roundworms of canids and felids, represent an important public health threat due to various disease manifestations in humans. Host recognition of pathogens is mediated by pattern recognition receptors (PRRs). Myeloid C-type lectin receptors (CLRs) are PRRs and recognise carbohydrate structures of various pathogens. As Toxocara excretory-secretory products (TES) are predominantly composed of glycoconjugates, they represent suitable targets for CLRs. However, the range of host-derived CLRs recognising Toxocara spp. is still unknown. Using a CLR-hFc fusion protein library, T. canis and T. cati L3 somatic antigens (TSOM) were bound by a variety of CLRs in enzyme-linked immunosorbent assay (ELISA), while their TES products interacted with macrophage galactose-type lectin-1 (MGL-1). Two prominent candidate CLRs, MGL-1 and macrophage C-type lectin (MCL), were selected for further binding studies. Immunofluorescence microscopy revealed binding of MGL-1 to the oral aperture of L3. Immunoblot experiments identified distinct protein fractions representing potential ligands for MGL-1 and MCL. To evaluate how these interactions influence the host immune response, bone marrow-derived dendritic cell (BMDC) assays were performed, showing MCL-dependent T. cati-mediated cytokine production. In conclusion, MGL-1 and MCL are promising candidates for immune modulation during Toxocara infection, deserving further investigation in the future.

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Cytokine production and signalling in human THP-1 macrophages is dependent on Toxocara canis glycans

Cited by 18 publications

References 73 publications

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

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

LPS Inhibits Fatty Acid Absorption in Enterocytes through TNF-α Secreted by Macrophages

Toxocara canis and Toxocara cati Somatic and Excretory-Secretory Antigens Are Recognised by C-Type Lectin Receptors

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