Information transfer in mammalian glycan-based communication

Glycan-binding proteins, so-called lectins, are exposed on mammalian cell
surfaces and decipher the information encoded within glycans translating
it into biochemical signal transduction pathways in the cell. These
glycan-lectin communication pathways are complex and difficult to analyze.
However, quantitative data with single -cell resolution provide means to
disentangle the associated signaling cascades. We chose C-type lectin
receptors (CTLs) expressed on immune cells as a model system to study
their capacity to transmit information encoded in glycans of incoming
particles. In particular, we used NF-κBnuclear factor kappa-B-reporter
cell lines expressing DC-specific ICAM-3–grabbing nonintegrin
(DC-SIGN)DC-SIGN, macrophage C-type lectin (MCL), dectin-1, dectin-2, and
minclemacrophage-inducible C-type lectin (MINCLE), as well as TNFαR and
TLR-1&2 in monocytic cell lines and compared their transmission of
glycan-encoded information. All receptors did transmit information with
similar signaling capacity, except dectin-2. This lectin was identified to
be less efficient in information transmission compared to the other CTLs,
and even while en the sensitivity of the dectin-2 pathway was enhanced by
overexpression of its co-receptor FcRγ, its transmitted information was
not. Next, we expanded our investigation towards the integration of
multiple signal transduction pathways including synergistic lectins, which
is crucial during pathogen recognition. We show how the signaling capacity
of lectin receptors using a similar signal transduction pathway (dectin-1
and dectin-2) areis being integrated by compromising between the lectins.
In contrast, co-expression of MCL synergistically enhanced the dectin-2
signaling capacity, particularly at low -glycan stimulant concentration.
By using dectin-2 and other lectins as examples, we demonstrate how
signaling capacity of dectin-2 is modulated in the presence of other
lectins, and therefore, the findings provide insight into how immune cells
translate glycan information using