CD14 is not involved in the uptake of synthetic CpG oligonucleotides

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.