Referee 2's review:

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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.
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The manuscript by Dan and colleagues report that CpG is synergistic with Cryptococcal neoformans mannoproteins when incubated with murine dendritic cells. These studies are important for understanding vaccine design especially with adjuvants.

1. The authors report their findings using TNF-alpha as a readout. However, there is little information about the role of TNF in vaccine-induced immunity. Is this cytokine important in vaccine-induced immunity to this fungus? If so, they should acknowledge this fact. If not, why did they choose it? Would IL-12 be a better focus than TNF? Although they do assess IL-12, it is subordinate to TNF. Moreover, what was the purpose of looking at certain chemokines? What was the rationale for selecting them?

2. They see an increase in IL-10 and IL-13, both anti-inflammatory cytokines. They state that the amounts produced were small. While that may be true that does not exclude the possibility that both modulate local immunity or even modulate the production of other cytokines. Does neutralization of IL-10 or IL-13 alter TNF or IL-12 generation?

3. Do TLR stimuli improve the responses in cells from MR knockout mice?

4. Why CpG 1826 and why 2336? A rationale should be given other than they are B and A odn.

5. Since IFN-alpha can down-regulate immunity would it not be appropriate to caution the reader that such a molecule would inhibit immune responses.