Curdlan activates dendritic cells through dectin-1 and toll-like receptor 4 signaling

Kim, Hyungsook; Park, Ki Hwan; Lee, Hong Kyung; Kim, Ji Sung; Kim, Yong Guk; Lee, Jae Hee; Kim, Ki Hun; Yun, Jieun; Hwang, Bang Yeon; Hong, Jin Tae; Kim, Youngsoo; Han, Sang‐Bae

doi:10.1016/j.intimp.2016.07.013

Cited by 60 publications

(34 citation statements)

References 40 publications

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“…PPRs consist of two classes of intracellular receptors: RIG-I-like receptors and NOD-like receptors; as well as two classes of plasma membrane receptors: TLRs and C-type lectin-like receptors. Dectin-1 is one of the best characterized PRRs with respect to β-glucan binding which belongs to the class of C-type lectin-like receptors and is reported to bind to zymosan, scleroglucan, schizophyllan, lentinan, curdlan and WGP [53,54,[56][57][58][59]. Dectin-1 is found on the surfaces of monocytes, macrophages, neutrophils, DCs, and T cells [60].…”

Section: β-Glucan Receptorsmentioning

confidence: 99%

Consumption of β-glucans to spice up T cell treatment of tumors: a review

Graaff

Govers

Wichers

et al. 2018

Expert Opinion on Biological Therapy

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Adoptive T-cell treatments of solid cancers have evolved into a robust therapy with objective response rates surpassing those of standardized treatments. Unfortunately, only a limited fraction of patients shows durable responses, which is considered to be due to a T cell-suppressive tumor microenvironment (TME). Here we argue that naturally occurring β-glucans can enable reversion of such T cell suppression by engaging innate immune cells and enhancing numbers and function of lymphocyte effectors. Areas covered: This review summarizes timely reports with respect to absorption, trafficking and immune stimulatory effects of β-glucans, particularly in relation to innate immune cells. Furthermore, we list effects toward well-being and immune functions in healthy subjects as well as cancer patients treated with orally administered β-glucans, extended with effects of β-glucan treatments in mouse cancer models. Expert opinion: Beta-glucans, when present in food and following uptake in the proximal gut, stimulate immune cells present in gut-associated lymphoid tissue and initiate highly conserved pro-inflammatory pathways. When tested in mouse cancer models, β-glucans result in better control of tumor growth and shift the TME toward a T cell-sensitive environment. Along these lines, we advocate that intake of β-glucans provides an accessible and immune-potentiating adjuvant when combined with adoptive T-cell treatments of cancer.

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Section: β-Glucan Receptorsmentioning

confidence: 99%

Consumption of β-glucans to spice up T cell treatment of tumors: a review

Graaff

Govers

Wichers

et al. 2018

Expert Opinion on Biological Therapy

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“…The Th1/ Th17 adjuvanticity of DMT 27 is controlled by the macrophageinducible Ca2 + -dependent lectin receptor (Mincle), whereas curdlan is a selective Dectin-1 agonist. 28 We first compared the immune responses of mice immunized with OVA alone or with CpG-B, curdlan, or DMT as adjuvant. As expected, spleen cells from mice immunized with OVA and CpG-B produced only IFN-γ after in vitro stimulation with OVA, whereas the splenocytes of mice that received OVA with either DMT or curdlan produced both IFN-γ and IL-17A ( Figure S1A).…”

Section: Resultsmentioning

confidence: 99%

IL-17 suppresses the therapeutic activity of cancer vaccines through the inhibition of CD8 ⁺ T-cell responses

et al. 2020

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Antitumor immunity is mediated by Th1 CD4 + and CD8 + T lymphocytes, which induce tumor-specific cytolysis, whereas Th17 CD4 + T cells have been described to promote tumor growth. Here, we explored the influence of IL-17 on the ability of therapeutic vaccines to induce the rejection of tumors in mice using several adjuvants known to elicit either Th1 or Th17-type immunity. Immunization of mice with Th1-adjuvanted vaccine induced high levels of IFN-γ-producing T cells, whereas injection with Th17promoting adjuvants triggered the stimulation of both IL-17 and IFN-γ-producing T cells. However, despite their capacity to induce strong Th1 responses, these Th17-promoting adjuvants failed to induce the eradication of tumors. In addition, the systemic administration of IL-17A strongly decreases the therapeutic effect of Th1-adjuvanted vaccines in two different tumor models. This suppressive effect correlated with the capacity of systemically delivered IL-17A to inhibit the induction of CD8 + T-cell responses. The suppressive effect of IL-17A on the induction of CD8 + T-cell responses was abolished in mice depleted of neutrophils, clearly demonstrating the role played by these cells in the inhibitory effect of IL-17A in the induction of antitumor responses. These results demonstrate that even though strong Th1-type responses favor tumor control, the simultaneous activation of Th17 cells may redirect or curtail tumor-specific immunity through a mechanism involving neutrophils. This study establishes that IL-17 plays a detrimental role in the development of an effective antitumor T cell response and thus could strongly affect the efficiency of immunotherapy through the inhibition of CTL responses.

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“…To accomplish these tasks, DCs must undergo maturation to express surface molecules pivotal for migration such as CCR7 and costimulatory molecules ( 14 , 17 ). Previous studies have already demonstrated that Curdlan can induce DC maturation ( 121 , 122 ), whereas the biological effect of Curdlan on Leishmania -infected DCs was unknown. Parasite harboring DCs show an enhanced Dectin-1 expression but are immature.…”

Section: Discussionmentioning

confidence: 99%

Dectin-1 Positive Dendritic Cells Expand after Infection with Leishmania major Parasites and Represent Promising Targets for Vaccine Development

et al. 2018

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Resistant mouse strains mount a protective T cell-mediated immune response upon infection with Leishmania (L.) parasites. Healing correlates with a T helper (Th) cell-type 1 response characterized by a pronounced IFN-γ production, while susceptibility is associated with an IL-4-dependent Th2-type response. It has been shown that dermal dendritic cells are crucial for inducing protective Th1-mediated immunity. Additionally, there is growing evidence that C-type lectin receptor (CLR)-mediated signaling is involved in directing adaptive immunity against pathogens. However, little is known about the function of the CLR Dectin-1 in modulating Th1- or Th2-type immune responses by DC subsets in leishmaniasis. We characterized the expression of Dectin-1 on CD11c+ DCs in peripheral blood, at the site of infection, and skin-draining lymph nodes of L. major-infected C57BL/6 and BALB/c mice and in peripheral blood of patients suffering from cutaneous leishmaniasis (CL). Both mouse strains responded with an expansion of Dectin-1+ DCs within the analyzed tissues. In accordance with the experimental model, Dectin-1+ DCs expanded as well in the peripheral blood of CL patients. To study the role of Dectin-1+ DCs in adaptive immunity against L. major, we analyzed the T cell stimulating potential of bone marrow-derived dendritic cells (BMDCs) in the presence of the Dectin-1 agonist Curdlan. These experiments revealed that Curdlan induces the maturation of BMDCs and the expansion of Leishmania-specific CD4+ T cells. Based on these findings, we evaluated the impact of Curdlan/Dectin-1 interactions in experimental leishmaniasis and were able to demonstrate that the presence of Curdlan at the site of infection modulates the course of disease in BALB/c mice: wild-type BALB/c mice treated intradermally with Curdlan developed a protective immune response against L. major whereas Dectin-1−/− BALB/c mice still developed the fatal course of disease after Curdlan treatment. Furthermore, the vaccination of BALB/c mice with a combination of soluble L. major antigens and Curdlan was able to provide a partial protection from severe leishmaniasis. These findings indicate that the ligation of Dectin-1 on DCs acts as an important checkpoint in adaptive immunity against L. major and should therefore be considered in future whole-organism vaccination strategies.

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Curdlan activates dendritic cells through dectin-1 and toll-like receptor 4 signaling

Cited by 60 publications

References 40 publications

Consumption of β-glucans to spice up T cell treatment of tumors: a review

Consumption of β-glucans to spice up T cell treatment of tumors: a review

IL-17 suppresses the therapeutic activity of cancer vaccines through the inhibition of CD8 ⁺ T-cell responses

Dectin-1 Positive Dendritic Cells Expand after Infection with Leishmania major Parasites and Represent Promising Targets for Vaccine Development

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Curdlan activates dendritic cells through dectin-1 and toll-like receptor 4 signaling

Cited by 60 publications

References 40 publications

Consumption of β-glucans to spice up T cell treatment of tumors: a review

Consumption of β-glucans to spice up T cell treatment of tumors: a review

IL-17 suppresses the therapeutic activity of cancer vaccines through the inhibition of CD8 + T-cell responses

Dectin-1 Positive Dendritic Cells Expand after Infection with Leishmania major Parasites and Represent Promising Targets for Vaccine Development

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IL-17 suppresses the therapeutic activity of cancer vaccines through the inhibition of CD8 ⁺ T-cell responses