Schistosoma mansoni worm glycolipids induce an inflammatory phenotype in human dendritic cells by cooperation of TLR4 and DC-SIGN

Stijn, Caroline M.W. van; Meyer, Sandra De; Broek, Marloes van den; Bruijns, Sven C. M.; Kooyk, Yvette van; Geyer, Rudolf; Die, Irma van

doi:10.1016/j.molimm.2010.01.014

Cited by 66 publications

(49 citation statements)

References 49 publications

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“…In schistosome infection, early proinflammatory responses may be due to adult worm and/or egg antigens ligating Toll-like receptors (TLRs) and C-type lectin receptors (CLRs) on macrophages (7)(8)(9). Among TLRs, TLR4 is unique, as it can generate both TIR domain-containing adapter-inducing IFN-␤ (TRIF)-and MyD88-dependent signaling cascades.…”

Section: S Chistosoma Mansoni Is a Helminth Parasite Of Humans That Bmentioning

confidence: 99%

“…In vitro studies show that antigens derived from egg and adult stages of S. mansoni can stimulate APCs to drive proinflammatory as well as anti-inflammatory responses via TLRs and C-type lectin receptors (CLRs) (9). Glycolipids from schistosomes can also activate dendritic cells via TLR4 and DC-SIGN to produce proinflammatory cytokines (8). This suggests that TLRs may be involved in recognition of helminth antigens to modulate macrophage activation in vivo.…”

Section: Fig 8 Granulomas Of Infected Cd14mentioning

confidence: 99%

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CD14 Influences Host Immune Responses and Alternative Activation of Macrophages during Schistosoma mansoni Infection

et al. 2014

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c Antigen-presenting cell (APC) plasticity is critical for controlling inflammation in metabolic diseases and infections. The roles that pattern recognition receptors (PRRs) play in regulating APC phenotypes are just now being defined. We evaluated the expression of PRRs on APCs in mice infected with the helminth parasite Schistosoma mansoni and observed an upregulation of CD14 expression on macrophages. Schistosome-infected Cd14 ؊/؊ mice showed significantly increased alternative activation of (M2) macrophages in the livers compared to infected wild-type (wt) mice. In addition, splenocytes from infected Cd14 ؊/؊ mice exhibited increased production of CD4 ؉ -specific interleukin-4 (IL-4), IL-5, and IL-13 and CD4 ؉ Foxp3 ؉ IL-10 ؉ regulatory T cells compared to cells from infected wt mice. S. mansoni-infected Cd14 ؊/؊ mice also presented with smaller liver egg granulomas associated with increased collagen deposition compared to granulomas in infected wt mice. The highest expression of CD14 was found on liver macrophages in infected mice. To determine if the Cd14 ؊/؊ phenotype was in part due to increased M2 macrophages, we adoptively transferred wt macrophages into Cd14 ؊/؊ mice and normalized the M2 and CD4 ؉ Th cell balance close to that observed in infected wt mice. Finally, we demonstrated that CD14 regulates STAT6 activation, as Cd14 ؊/؊ mice had increased STAT6 activation in vivo, suggesting that lack of CD14 impacts the IL-4R␣-STAT6 pathway, altering macrophage polarization during parasite infection. Collectively, these data identify a previously unrecognized role for CD14 in regulating macrophage plasticity and CD4 ؉ T cell biasing during helminth infection.

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Section: S Chistosoma Mansoni Is a Helminth Parasite Of Humans That Bmentioning

confidence: 99%

Section: Fig 8 Granulomas Of Infected Cd14mentioning

confidence: 99%

CD14 Influences Host Immune Responses and Alternative Activation of Macrophages during Schistosoma mansoni Infection

et al. 2014

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“…DC-SIGN is a C-type lectin receptor shown to be involved in DC maturation induced by apoptotic neutrophils and Schistosoma manosoni worm glycolipids (41,42). To examine the involvement of this lectin in DC maturation, we used two different neutralizing antibodies to block the receptor engagement.…”

Section: Both Cell-cell Contact and Soluble Factors Are Required Formentioning

confidence: 99%

“…Several endogenous ligands have been shown to activate members of the TLR family, and signaling via TLRs is known to induce DC maturation (43). TLR4 is one of the well studied members of this family and has been shown to cooperate with DC-SIGN to induce activation of human DCs (42). Therefore, we investigated the possibility of involvement of this receptor in DC maturation signaling.…”

Section: Both Cell-cell Contact and Soluble Factors Are Required Formentioning

confidence: 99%

Activated Apoptotic Cells Induce Dendritic Cell Maturation via Engagement of Toll-like Receptor 4 (TLR4), Dendritic Cell-specific Intercellular Adhesion Molecule 3 (ICAM-3)-grabbing Nonintegrin (DC-SIGN), and β2 Integrins

Pathak

Sköld

Mohanram

et al. 2012

Journal of Biological Chemistry

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Background: Activated apoptotic lymphocytes provide activation/maturation signals to human monocyte-derived dendritic cells (DCs). Results: Cell-cell contact-dependent signaling involved ␤2 integrins, DC-SIGN, and TLR4, which resulted in activation of multiple signaling pathways. Conclusion: These studies provide mechanistic insight into DC responses during encounter with cells undergoing immunogenic cell death. Significance: Learning how DCs respond to certain cell death has implications for vaccine design.

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“…Human DCs primed with adult worm glycolipids switch towards a Th1 immune response and induce an inflammatory cytokine cascade. DC-SIGN binds to fucose components of the glycolipid of the worm and helps activate TLR4 signalling and inflammation (van Stijn et al, 2010). It is proposed that DC-SIGN recruits glycolipids and then presents them to TLR4, via a TLR4-DC-SIGN complex in lipid rafts.…”

Section: Recognition Of Schistosoma Mansoni By Prrsmentioning

confidence: 99%

Pattern Recognition Receptors and Infectious Diseases

Jopeace¹,

Howard²,

Murton³

et al. 2012

Insight and Control of Infectious Disease in Global Scenario

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Schistosoma mansoni worm glycolipids induce an inflammatory phenotype in human dendritic cells by cooperation of TLR4 and DC-SIGN

Cited by 66 publications

References 49 publications

CD14 Influences Host Immune Responses and Alternative Activation of Macrophages during Schistosoma mansoni Infection

CD14 Influences Host Immune Responses and Alternative Activation of Macrophages during Schistosoma mansoni Infection

Activated Apoptotic Cells Induce Dendritic Cell Maturation via Engagement of Toll-like Receptor 4 (TLR4), Dendritic Cell-specific Intercellular Adhesion Molecule 3 (ICAM-3)-grabbing Nonintegrin (DC-SIGN), and β2 Integrins

Pattern Recognition Receptors and Infectious Diseases

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