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. 2020 Feb 21;201(1):14–24. doi: 10.1111/cei.13426

Figure 2.

Figure 2

Toll‐like receptor (TLR)‐stimulation ability depends on the polycation–DNA complex structure, which influences the packaging of the DNA and the inter‐DNA spacing of contiguous DNA molecules. (a) Schematic representation of a structural type of DNA–polycation complex: cationic molecules bind and organize DNA chains (blue cylinders) into a columnar structure with a short‐ranged order. (b) Hypothetical structure of TLR‐9 and its interaction with dsDNA. (c) The optimal geometric spacing (inter‐DNA distance) between ordered dsDNA molecules bound to chemokine C‐X‐C ligand motif (CXCL4) [or other polycations, such as LL‐37 or human β‐defensin (HBD3)] is in the range between 3 and 4 nm (d). This amplitude almost matches the steric size of TLR‐9 and allows activate multiple TLR‐9 at the same time leading to the optimal interferon (IFN)‐α production. Outside this range (d smaller or larger than 3–4 nm), stimulation results in a modest or no IFN‐α production.