Combined TLR2 and TLR4 ligation in the context of bacterial or helminth extracts in human monocyte derived dendritic cells: molecular correlates for Th1/Th2 polarization

Riet, Elly van; Everts, Bart; Retra, Kim; Phylipsen, Marion; Hellemond, Jaap J. van; Tielens, Aloysius G.M.; Kleij, Desirée van der; Hartgers, Franca C.; Yazdanbakhsh, Maria

doi:10.1186/1471-2172-10-9

Cited by 78 publications

(74 citation statements)

References 62 publications

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“…Our findings correlate with other studies on dendritic cells, as Schistosoma mansoni egg Ags reduce LPS-stimulated phosphorylation of p38, JNK, and ERK in murine dendritic cells (44). S. haematobium and Ascaris lumbricoides infections were shown to suppress LPS-induced p38 phosphorylation, but not ERK activation, in dendritic cells (45,46). Studies demonstrate that NF-kB 2/2 mice infected with Trichuris muris show increased susceptibility to infection, with impaired Th2/Treg immune responses and the phosphorylation of NF-kB and ERK supposed to be crucial in helminth-induced Th2 immune responses (47,48).…”

Section: Discussionsupporting

confidence: 81%

Fasciola hepatica Tegumental Coat Impairs Mast Cells’ Ability To Drive Th1 Immune Responses

Vukman

Adams

Metz

et al. 2013

The Journal of Immunology

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The parasitic worm Fasciola hepatica induces strong Th2 and T-regulatory immune responses while simultaneously suppressing Th1-driven immune responses to bystander microbial infections. It also prevents the initiation of Th1-mediated autoimmune disorders in mice through the suppression of Th17 and Th1 immune responses, and this can be mimicked by parasite-derived molecules. We have isolated F. hepatica tegumental coat Ag (FhTeg) and demonstrated its suppressive effect in vivo by directly targeting dendritic cells, impairing their ability to drive Th1 responses. Mast cells are critical in promoting Th1 protective immunity during bacterial infection and in driving Th1-mediated pathological conditions in autoimmune diseases. In this article, we show that FhTeg inhibits the ability of mast cells to drive the Th1 immune response by suppressing cytokine secretion (TNF-α, IL-6, IFN-γ, and IL-10) and ICAM1 expression in mast cells stimulated with LPS or heat-inactivated Bordetella pertussis Ag. These heat-inactivated B. pertussis Ag/LPS–stimulated mast cells fail to promote Th1 immune responses in CD4+ T cells when pretreated with FhTeg, and a role for ICAM1 in this process was demonstrated. FhTeg suppresses the activation of transcription factors in the TLR signaling pathway, which explains the decrease in cytokine production and cell surface marker expression. We demonstrated that FhTeg suppresses MAPK and NF-κB activation and enhances SOCS3 expression, which could explain its negative effect on the TLR pathways. We conclude that FhTeg targets innate immune cells, inhibiting their ability to drive Th1 immune responses.

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Section: Discussionsupporting

confidence: 81%

Fasciola hepatica Tegumental Coat Impairs Mast Cells’ Ability To Drive Th1 Immune Responses

Vukman

Adams

Metz

et al. 2013

The Journal of Immunology

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“…TLR have previously been shown to be involved in S. mansoni antigen recognition by DC [12,[14][15][16][17], and for this reason, we analyzed TLR expression in CD4 1 T cells from NOD and C57BL/6 mice. We found that both the mRNA and surface protein levels of TLR1 and TLR6 are significantly higher in NOD mouse CD4 1 T cells ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…1). Taking into considera- tion the involvement of TLR2 [12,[14][15][16][17] in S. mansoniinduced immunomodulation, the disparate response by NOD and C57BL/6 CD4 1 T cells to TLR2 ligation may provide a partial explanation for the differential response to SEA in the two strains.…”

Section: Resultsmentioning

confidence: 99%

“…In this study, we highlighted the importance of CLR and TLR in the T-cell response we observed to SEA. Schistosome-derived products have been shown to bind both CLR and TLR on APC with roles identified for both TLR2 and DC-SIGN in the human and TLR2 in mice [14][15][16][17]26]. In this study, we provided evidence that in addition to its effects on DC, SEA also mediated effects directly on CD4 1 T cells, inducing surface-bound LAP and expression of the CLR DEC-205 and galectin-3 on T cells from NOD but not C57BL/6 mice ( Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The modulation of TLR signaling by S. mansoni antigen has been most widely studied on DC and MF [9][10][11][12][13]. TLR2 has been shown to recognize molecules within SEA [14,15], and it has been suggested that it may participate in the control of immunopathology during S. mansoni infection, in part through effects on the priming and expansion of Treg [16]. However, another report found that TLR2 appears to be dispensable in the control of pathology and infection [17], and TLR2 has been shown not to be required to modulate the activation of DC or their ability to induce a Th2 response [18,19].…”

Section: Introductionmentioning

confidence: 99%

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Importance of TLR2 in the direct response of T lymphocytes to Schistosoma mansoni antigens

et al. 2010

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The immunomodulatory effect of Schistosoma mansoni antigens has often been attributed to interaction with PRR expressed on APC. Our previous work has shown that S. mansonisoluble egg antigen (SEA) can induce, together with a Th2 response, TGF-b-dependent Foxp3 expression in naïve CD4 1 T cells from NOD mice. We found that SEA can directly upregulate the expression of surface-bound TGF-b in purified CD4 1 T cells in the absence of accessory cell interactions. In this study, we show that the C-type lectin receptors DEC-205 and galectin-3 were involved in the direct interaction between S. mansoni antigens and CD4 1 T cells. SEA was able to enhance CD4 1 T-cell secretion of bioactive TGF-b in response to TLR2 ligand stimulation, in the absence of APC. We also show that TLR2 expressed on CD4 1 T cells was important for the Foxp3 expression induced by SEA.

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Ecoimmunology in the field: Measuring multiple dimensions of immune function with minimally invasive, field‐adapted techniques

Blackwell

García

2022

American J Hum Biol

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Immune function is multifaceted and characterizations based on single biomarkers may be uninformative or misleading, particularly when considered across ecological contexts. However, measuring the many facets of immunity in the field can be challenging, since many measures cannot be obtained on-site, necessitating sample preservation and transport. Here we assess state-of-the-art methods for measuring immunity, focusing on measures that require a minimal blood sample obtained from a finger prick, which can be: (1) dried on filter paper, (2) frozen in liquid nitrogen, or (3) stabilized with chemical reagents. Results:We review immune measures that can be obtained from point-of-care devices or from immunoassays of dried blood spots (DBSs), field methods for flow cytometry, the use of RNA or DNA sequencing and quantification, and the application of immune activation assays under field conditions. Conclusions: Stable protein products, such as immunoglobulins and C-

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Combined TLR2 and TLR4 ligation in the context of bacterial or helminth extracts in human monocyte derived dendritic cells: molecular correlates for Th1/Th2 polarization

Cited by 78 publications

References 62 publications

Fasciola hepatica Tegumental Coat Impairs Mast Cells’ Ability To Drive Th1 Immune Responses

Fasciola hepatica Tegumental Coat Impairs Mast Cells’ Ability To Drive Th1 Immune Responses

Importance of TLR2 in the direct response of T lymphocytes to Schistosoma mansoni antigens

Ecoimmunology in the field: Measuring multiple dimensions of immune function with minimally invasive, field‐adapted techniques

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