Flexible Signaling of Myeloid C-Type Lectin Receptors in Immunity and Inflammation

Myeloid C-type lectin receptors (CLRs) are important sensors of self and non-self that work in concert with other pattern recognition receptors (PRRs). CLRs have been previously classified based on their signaling motifs as activating or inhibitory receptors. However, specific features of the ligand binding process may result in distinct signaling through a single motif, resulting in the triggering of non-canonical pathways. In addition, CLR ligands are frequently exposed in complex structures that simultaneously bind different CLRs and other PRRs, which lead to integration of heterologous signaling among diverse receptors. Herein, we will review how sensing by myeloid CLRs and crosstalk with heterologous receptors is modulated by many factors affecting their signaling and resulting in differential outcomes for immunity and inflammation. Finding common features among those flexible responses initiated by diverse CLR-ligand partners will help to harness CLR function in immunity and inflammation.CF is supported by AECC Foundation as recipient of an ``Ayuda Fundacion Cientifica AECC a personal investigador en cancer.´´ SI is funded by grant SAF2015-74561-JIN from the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and European Fund for Regional Development (FEDER). PS-L is funded by grant BES-2015-072699 (´´Ayudas para contratos predoctorales para la formacion de doctores 2015´´) from MINECO. MM-L received a FPU fellowship (AP2010-5935) from the Spanish Ministry of Education. Work in the DS laboratory is funded by the CNIC and grant SAF2016-79040-R from MINECO and FEDER; B2017/BMD-3733 Immunothercan-CM from Comunidad de Madrid; RD16/0015/0018-REEM from FIS-Instituto de Salud Carlos III, MINECO, and FEDER; Foundation Acteria; Constantes y Vitales prize (Atresmedia); Foundation La Marato de TV3 (201723); the European Commission (635122-PROCROP H2020); and the European Research Council (ERC-Consolidator Grant 725091). The CNIC is supported by the MINECO and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). The authors have no conflicting financial interests.S