Targeting Syk-Card9-activating C-type lectin receptors by vaccine adjuvants: Findings, implications and open questions

Pathogen recognition by the innate immune system is essential for the induction of adaptive T cell responses. A diverse range of pathogen-associated molecular patterns (PAMPs) are recognized by a variety of pathogen recognition receptors (PRRs). Among these are the well known Toll-like receptors (TLR) and the more recently described C-type lectin receptors (CLR) which utilize distinct signaling pathways leading to a diverse repertoire of effector molecules produced. The composition of the inflammatory juice released from activated innate immune cells has a major impact on the polarization of Th cell responses. Defined PAMPs may therefore be used as adjuvants to direct adaptive immune responses to subunit vaccines. Targeting CLR is an alternative or complementary strategy to TLR-triggering adjuvants that will benefit the development of more efficient subunit vaccines for prevention of major human infectious diseases. In this short review, we discuss the potential of CLRs activating APC via the Syk-Card9 pathway as receptors for adjuvants that direct the development of robust Th17 and Th1 responses to subunit vaccines.