Referee 1's review (Mihai Netea):

**********
N.B. These are the comments made by the referee when reviewing an earlier version of this paper. Prior to publication, the manuscript has been revised in light of these comments and to address other editorial requirements.
**********

The manuscript by Dan and colleagues investigates the synergistic role of MR and TLR engagement for the stimulation of cytokine production by DCs. The subject of collaboration between lectin receptors and TLRs is very relevant and the data are novel. The experiments are well designed and the manuscript is clearly written.

Comments:

1. Several stimuli were prepared by the authors, while other have been purchased (e.g. Saccharomyces mannan). How did the authors ensure that no contamination (for example with LPS) was present in the preparations? While the absence of certain effects in MR-deficient cells supports the conclusions of the authors, an LAL assay or other way of excluding LPS contamination would be reassuring.

2. The parameter chosen by the authors is cytokine production. However, other functions of DCs are equally important for DC maturation and T-cell stimulation, such as expression of adhesion molecules. Did the authors attempted to assess the effect of MR/TLR stimulation on these additional parameters?

3. Interestingly, as authors also discuss, the stimulation of some cytokines such as IL-2 by mannan seems to be MR-independent, while the synergistic effect is MR-dependent. DC-SIGN and TLR4 receptors were named by the authors as additional mannan receptors. Do they account for the MR-independent effects of mannan and mannoproteins?