We have previously shown that DEC205, a surface receptor expressed at high levels on CD8+DC, is able to
capture synthetic CpG oligonucleotides (ODN) and is required for optimal responsiveness. However, even
in the absence of DEC205, CD8+DC are able to respond to CpG ODN, albeit suboptimally. This suggested
that additional receptors might contribute to the uptake of CpG ODN. CD14 represented an ideal candidate
as it is expressed by DC and has been shown to bind and facilitate the uptake of CpG ODN. However,
when CD14-deficient (CD14−/−) mice and normal B6 mice were injected with CpG ODN, CD8+DC were
equivalently activated as assessed by the upregulation of the co-stimulatory molecules CD40 and CD80.
Furthermore, the level of serum IL-6 and IL-12 produced in response to CpG ODN was comparable in
CD14−/− and B6 mice. Importantly, mice deficient in both DEC205 and CD14 had comparable responses
to mice lacking DEC205 alone, both in terms of cytokine production and DC activation, arguing that CD14
did not contribute to responses to CpG ODN. For CD14 to act as an uptake receptor for CpG ODN, it
must first capture CpG ODN. To this end we assessed the capacity of cell surface CD14 to bind CpG ODN.
Although we unequivocally confirmed that CD14 is required for the binding of its known ligand LPS, CD14
was not required for binding or responses to A-, B-, and C- Class CpG ODN. Our studies dispute the claim
that CD14 is involved in CpG ODN capture.