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C‐type lectin receptors MR and DC‐SIGN are involved in recognition of hemocyanins, shaping their immunostimulatory effects on human dendritic cells
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Villar, Javiera, Salazar, Michelle L., Jiménez, José M., Campo, Miguel Del, Manubens, Augusto, Gleisner, María Alejandra, Ávalos, Ignacio, Salazar‐Onfray, Flavio, Salazar, Fabián, Mitchell, Daniel A., Alshahrani, Mohammad Y., Martínez‐Pomares, Luisa and Becker, María Inés (2021) C‐type lectin receptors MR and DC‐SIGN are involved in recognition of hemocyanins, shaping their immunostimulatory effects on human dendritic cells. European Journal of Immunology, 51 (7). pp. 1715-1731. doi:10.1002/eji.202149225 ISSN 1521-4141.
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Official URL: http://dx.doi.org/10.1002/eji.202149225
Abstract
Hemocyanins are used as immunomodulators in clinical applications because they induce a strong Th1-biased cell-mediated immunity, which has beneficial effects. They are multiligand glycosylated molecules with abundant and complex mannose-rich structures. It remains unclear whether these structures influence hemocyanin-induced immunostimulatory processes in human APCs. We have previously shown that hemocyanin glycans from Concholepas concholepas (CCH), Fissurella latimarginata (FLH), and Megathura crenulata (KLH), participate in their immune recognition and immunogenicity in mice, interacting with murine C-type lectin receptors (CLRs). Here, we studied the interactions of these hemocyanins with two major mannose-binding CLRs on monocyte-derived human DCs: MR (mannose receptor) and DC-SIGN (DC-specific ICAM-3–grabbing nonintegrin). Diverse analyses showed that hemocyanins are internalized by a mannose-sensitive mechanism. This process was calcium dependent. Moreover, hemocyanins colocalized with MR and DC-SIGN, and were partly internalized through clathrin-mediated endocytosis. The hemocyanin-mediated proinflammatory cytokine response was impaired when using deglycosylated FLH and KLH compared to CCH. We further showed that hemocyanins bind to human MR and DC-SIGN in a carbohydrate-dependent manner with affinity constants in the physiological concentration range. Overall, we showed that these three clinically valuable hemocyanins interact with human mannose-sensitive CLRs, initiating an immune response and promoting a Th1 cell-driving potential.
Item Type: | Journal Article | ||||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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SWORD Depositor: | Library Publications Router | ||||||||
Journal or Publication Title: | European Journal of Immunology | ||||||||
Publisher: | Wiley | ||||||||
ISSN: | 1521-4141 | ||||||||
Official Date: | 2 July 2021 | ||||||||
Dates: |
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Volume: | 51 | ||||||||
Number: | 7 | ||||||||
Page Range: | pp. 1715-1731 | ||||||||
DOI: | 10.1002/eji.202149225 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Restricted or Subscription Access |
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