The IFN-b-inducing effect of c-di-AMP contributes, at least in part, to the reported proliferation of antigen-specific T cell types and the evolvement of the proposed balanced TH1/TH2/TH17 cell response. DC subset targeting was investigated also with regard to the c-di-AMPinduced IFN-b production. Conventional DCs showed a much more pronounced IFN-b production than plasmacytoid DCs. This finding was somewhat surprising because plasmacytoid DCs are known to be specialized in IFN type I production and usually produce these IFNs in much higher amounts than conventional DCs, which are specialized in antigen presentation. By targeting conventional DCs, c-di-AMP evokes the secretion of a rather limited amount of IFN-b which may be important to fine tune immune responses. Interestingly, also the IFN-b response to L. monocytogenes was reported not to be mediated by plasmacytoid DCs either. Since it is known that the bacterium secretes c-di-AMP in the course of infection, our results further strengthen the suggestion that c-di-AMP is indeed the mediator of the L. monocytogenes-induced IFN-b. The modes of action described here do not exclude additional, not yet identified mechanisms of c-di-AMP-mediated immune response modulation. For example, other co-stimulatory molecules or secreted immune signaling molecules could be regulated in a cdi-AMP-dependent manner to enhance or modulate antigeninduced immune responses by acting on either effector or bystander cells. However, our results further elucidate intermediate steps of the immune response cascade leading to the immune modulatory activity of c-di-AMP observed in immunization studies on mice. They advance the knowledge on modes of adjuvant action toward the regulation of effective immunization responses. Transcription Activator-Like Effectors technology comprises a rapidly developing tool for targeted genome manipulation. Deciphering of the TALE DNA recognition code in 2009 led to the development of a series of novel engineered TALE chimeras for a variety of purposes. For example, TALEs have been engineered to modulate gene expression, reprogram epigenetic modifications, repair or disrupt genes using TALENs or chimeric TALE recombinases, and promote targeted gene transposition using TALE-directed piggyBac. TALEs offer an attractive advantage over traditional zinc finger-based technologies due to their inherently simple and predictable DNA recognition code attributed to its novel type DNA-binding domain. The TALE DBD is highly repetitive and contains a tandem array of repeat monomers with each monomer consisting of,34 amino acids with the exception of the last repeat unit consisting of,20 amino acids. Relative to TALENs, the potential of TALEs as activators has not been fully explored until more recently. Initial studies showed that a single TALE activator was able to drive the expression of a reporter gene linked to a synthetic promoter derived from different cellular genes.