Linking Viral DNA to Endosomal Innate Immune Recognition

Activation of the adaptive immune system has long been known to depend on two signals: Ag specificity alone is not enough, but is cross-checked for the presence of a second, independent signal confirming the irregularity of the first Ag-specific signal. Prominent examples are B cell responses that are controlled by Th cells specific for the same Ag, or T cell responses that are controlled through the presence of activated APCs, typically caused by infections. In this regard, infections are recognized by distinct signals, such as pathogen-associated structural patterns (1), including Ag repetitiveness, which is mostly recognized by B cells and the humoral innate immune system, as well as by pathogen-associated molecular patterns, recognized by cell surface, endosomal, and intracellular receptors (2). Most intuitive ligands for these receptors, such as LPS, only exist in bacterial outer membranes and are recognized, in this case, by TLR4 on the...