not sugars. If and when the ligand is sugar they need Ca2+ – hence the name "C-type", but many of them don't even have a known sugar ligand thus despite carrying a lectin type fold structure, some of them are technically not "lectin" in function. CLR signaling There are several types of signaling involved in CLRs induced immune response, major connection has been identified between TLR and CLR signaling, therefore we differentiate between TLR-dependent and TLR-independent signaling. DC-SIGN leading to RAF1-MEK-ERK cascade, BDCA2 signaling via ITAM and signaling through ITIM belong among the TLR-dependent signaling. TLR-independent signaling such as Dectin 1, and Dectin 2 - mincle signaling lead to MAP kinase and NFkB activation. Membrane receptor CLRs have been divided into 17 groups based on structure and phylogenetic origin. Generally there is a large group, which recognizes and binds carbohydrates, so called carbohydrate recognition domains (CRDs) and the previously mentioned CTLDs. Another potential characterization of the CLRs can be into mannose receptors and asialoglycoprotein receptors. Group I CLRs: The mannose receptors The mannose receptor (MR) is a PRR primarily present on the surface of macrophages and dendritic cells. It belongs into the calcium-dependent multiple CRD group. The MR belongs to the multilectin receptor protein group and, like the TLRs, provides a link between innate and adaptive immunity. It recognizes and binds to repeated mannose units on the surfaces of infectious agents and its activation triggers endocytosis and phagocytosis of the microbe via the complement system. Specifically, mannose binding triggers recruitment of MBL-associated serine proteases (MASPs). The serine proteases activate themselves in a cascade, amplifying the immune response: MBL interacts with C4, binding the C4b subunit and releasing C4a into the bloodstream; similarly, binding of C2 causes release of C2b. Together, MBL, C4b and C2a are known as the C3 convertase. C3 is cleaved into its a and b subunits, and C3b binds the convertase. These together are called the C5 convertase. Similarly again, C5b is bound and C5a is released. C5b recruits C6, C7, C8 and multiple C9s. C5, C6, C7, C8 and C9 form the membrane attack complex (MAC). Group II CLRs: asialoglycoprotein receptor family This is another large superfamily of CLRs that includes the classic asialoglycoprotein receptor macrophage galactose-type lectin (MGL), DC-SIGN (CLEC4L), Langerin (CLEC4K), Myeloid DAP12‑associating lectin (MDL)‑1 (CLEC5A), DC‑associated C‑type lectin 1 (Dectin1) subfamily, and DC immunoreceptor (DCIR) subfamily. Furthermore, Dectin subfamily and DCIR subfamily consist