TLR2- and 4-independent immunomodulatory effect of high molecular weight components from Ascaris suum

Favoretto, Bruna C.; Silva, Sandriana R.; Jacysyn, Jacqueline de Fátima; Câmara, Niels Olsen Saraiva; Faquim-Mauro, Eliana L.

doi:10.1016/j.molimm.2013.10.011

Cited by 7 publications

(8 citation statements)

References 52 publications

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“…Also, PI downmodulate the DC maturation induced by ligands of TLR2, TLR3, or TLR4. Furthermore, we verified that TLR2 and TLR4 are not involved in the modulatory effect of PI on DCs [ 53 ].…”

Section: Discussionmentioning

confidence: 63%

Crotoxin Isolated fromCrotalus durissus terrificusVenom Modulates the Functional Activity of Dendritic Cells via Formyl Peptide Receptors

Freitas

Favoretto

Clissa

et al. 2018

Journal of Immunology Research

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The Crotalus durissus terrificus rattlesnake venom, its main toxin, crotoxin (CTX), and its crotapotin (CA) and phospholipase A2 (CB) subunits modulate the immune system. Formyl peptide receptors (FPRs) and lipoxin A4 (LXA4) are involved in CTX's effect on macrophages and neutrophils. Dendritic cells (DCs) are plasticity cells involved in the induction of adaptive immunity and tolerance maintenance. Therefore, we evaluated the effect of CTX, CA or CB on the maturation of DCs derived from murine bone marrow (BM). According to data, CTX and CB—but not CA—induced an increase of MHC-II, but not costimulatory molecules on DCs. Furthermore, CTX and CB inhibited the expression of costimulatory and MHC-II molecules, secretion of proinflammatory cytokines and NF-κBp65 and p38/ERK1/2-MAPK signaling pathways by LPS-incubated DCs. Differently, CTX and CB induced IL-10, PGE2 and LXA4 secretion in LPS-incubated DCs. Lower proliferation and IL-2 secretion were verified in coculture of CD3+ cells and DCs incubated with LPS plus CTX or CB compared with LPS-incubated DCs. The effect of CTX and CB on DCs was abolished in cultures incubated with a FPRs antagonist. Hence, CTX and CB exert a modulation on functional activity of DCs; we also checked the involvement the FPR family on cell activities.

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Section: Discussionmentioning

confidence: 63%

Crotoxin Isolated fromCrotalus durissus terrificusVenom Modulates the Functional Activity of Dendritic Cells via Formyl Peptide Receptors

Freitas

Favoretto

Clissa

et al. 2018

Journal of Immunology Research

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“…Similarly, Favoretto et al. (2014) demonstrated that high molecular weight components (P1) isolated from A. suum extract similarly suppressed upregulation of CD80 and CD86 by murine bmDC following ligation of TLR 1/2, 3 or 4 ( 13 ). Expression of the co-stimulatory molecule CD40 and MHC-II were also suppressed in this model.…”

Section: Discussionmentioning

confidence: 96%

“…Here we investigated the impact of Ascaris E/S on the functions of porcine DC, hence examining potential modulation of immune cells from the parasite’s definitive host species. Previous studies have examined immunomodulation of murine bmDC by A. suum extract ( 13 ) and pseudocoelomic body fluid (ABF) from the closely-related A. lumbricoides ( 12 ), as well as of human moDC by A. suum ABF ( 14 , 15 ). While this data provided hints to possible modulatory effects of Ascaris exposure on DC phenotypes in vivo , several limitations exist.…”

Section: Discussionmentioning

confidence: 99%

“…Prior research targeting the immunomodulatory effects of Ascaris and DC primarily relied on the use of murine bone marrow-derived (bmDC) ( 12 , 13 ) and human monocyte-derived DC (moDC) ( 14 , 15 ) generated in vitro . bmDC exhibit an immature phenotype in comparison to peripheral blood DC ( 16 ), whereas moDC differentiate from monocytes in vivo at sites of inflammation, but are not present during steady-state conditions ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

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Ascaris suum excretory/secretory products differentially modulate porcine dendritic cell subsets

Hamid

Ebner²,

Bechtold³

et al. 2022

Front. Immunol.

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Helminths produce excretory/secretory products (E/S) which can modulate the immune responses of their hosts. Dendritic cells (DC) are essential for initiating the host T cell response and are thus potential targets for modulation by helminth E/S. Here we study immunomodulation of porcine peripheral blood DC subsets following ex vivo stimulation with E/S from Ascaris suum, a common helminth of pigs with considerable public health and economic importance. Our data showed that the relative frequencies of DC subsets in porcine blood differ, with plasmacytoid DC (pDC) being the most prominent in healthy 6-month-old pigs. pDC are an important cytokine source, and we found that A. suum E/S suppressed production of the type 1 cytokines IL-12p40 and TNF-α by this subset following toll-like receptor (TLR) ligation. In contrast, conventional DC (cDC) are more efficient antigen presenters, and the expression of CD80/86, costimulatory molecules essential for efficient antigen presentation, were modulated differentially by A. suum E/S between cDC subsets. CD80/86 expression by type 1 cDC (cDC1) following TLR ligation was greatly suppressed by the addition of A. suum E/S, while CD80/86 expression by type 2 cDC (cDC2) was upregulated by A. suum E/S. Further, we found that IFN-γ production by natural killer (NK) cells following IL-12 and IL-18 stimulation was suppressed by A. suum E/S. Finally, in the presence of E/S, IFN-γ production by CD4+ T cells co-cultured with autologous blood-derived DC was significantly impaired. Together, these data provide a coherent picture regarding the regulation of type 1 responses by A. suum E/S. Responsiveness of pDC and cDC1 to microbial ligands is reduced in the presence of E/S, effector functions of Th1 cells are impaired, and cytokine-driven IFN-γ release by NK cells is limited.

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“…Os helmintos e alguns de seus produtos exercem importante efeito modulador no sistema imune (FAQUIM-MAURO;MACEDO, 1998;revisado por FINKELMAN et al, 1991;HAIG;LIMA;MOTA, 1980;SILVA et al, 2006). Neste contexto, nós temos estudado o mecanismo imunomodulador de antígenos de alta massa molecular do extrato de Asc (FAVORETTO et al, 2014).…”

Section: Discussionunclassified

Estudo da participação dos receptores DC-SIGN e MR nos mecanismos de supressão da resposta imune induzida por componentes de alta massa molecular do extrato de Ascaris suum.

Favoretto¹

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Molecules with immunomodulatory properties have been investigated and represent useful tools for understanding the mechanisms involved in the activation and control of immune responses. High molecular weight components (PI) of Ascaris suum extract exert suppressive effect on the immune response to homologous and heterologous antigens, such as ovalbumin (OVA). The PI components exert direct effect on antigen presenting cells (APCs), as dendritic cells (DCS), inhibiting the expression of molecules involved in antigen presentation and thus, decreasing the T lymphocyte proliferation. In addition, this effect is independent of Toll-like receptors 2 and 4 (TLR2 and 4) as well as MyD88 molecule. In this work we studied the glycoconjugates in PI and the participation of C-type lectin receptors (CLRs), mainly the DC-SIGN and MR, in the modulation of the functional activity of DCs. The analysis of anion exchange chromatography (HPAEC-PAD) and mass spectrometry (UV-MALDI-TOF) show that PI components contain high mannose-and complextype N-linked oligosaccharides and phosphorylcholine residues. The binding affinity with distinct lectins showed that part of PI presented affinity to Canavalia ensiformis (ConA), however did not bind to Artocarpus integrifolia (jacalina) suggesting that antigens containing N-linked glycans are abundant in PI. It was observed by flow cytometry that the PI components containing N-linked glycans inhibited the DCs maturation induced by LPS. On the other hand, the previous incubation of DCs with mannan, anti-DC-SIGN and/or anti-MR antibodies abolished the modulatory effect of PI on the DCs maturation. Furthermore, analysys of flow cytometry and confocal microscopy showed that the high binding and internalization of PI-Alexa by DCs was decreased when the cells were previously incubated with mannan, anti-DC-SIGN and/or anti-MR antibodies. It was also observed that the blockage of DC-SIGN and MR in DCs reversed the inhibitory effect of PI in the in vitro T cells proliferative response. Taking together these results show the involvement of DC-SIGN and MR in the recognition of N-glycosylated components of PI by DCs and in its modulatory effect.

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TLR2- and 4-independent immunomodulatory effect of high molecular weight components from Ascaris suum

Cited by 7 publications

References 52 publications

Crotoxin Isolated fromCrotalus durissus terrificusVenom Modulates the Functional Activity of Dendritic Cells via Formyl Peptide Receptors

Crotoxin Isolated fromCrotalus durissus terrificusVenom Modulates the Functional Activity of Dendritic Cells via Formyl Peptide Receptors

Ascaris suum excretory/secretory products differentially modulate porcine dendritic cell subsets

Estudo da participação dos receptores DC-SIGN e MR nos mecanismos de supressão da resposta imune induzida por componentes de alta massa molecular do extrato de Ascaris suum.

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