Tunicate Lectins as Acute Phase Reactants in Innate Immunity

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From the early studies on invertebrate lectins, their designation as 'protectins' was proposed to suggest that, because invertebrates lack adaptive immunity mediated by immunoglobulins, B and T cells, these proteins would mediate internal protection for the adult or its eggs against microbial or fungal infection. The modern era of research on animal lectins has seen a vast expansion on these foundations, to find lectins from vertebrates in direct participation in innate immune functions, as LPS-binding molecules, opsonins, and complement-activating factors. Numerous lectins with immune-related functions have been described, particularly among the C-type, lectins that require Ca++ in their carbohydrate-recognition domain (CRD) for binding to ligand, and share a CRD sequence motif. Recently, some members of the galectin family, another major structural class of lectins which do not require Ca++ for binding and share a different CRD motif, have been proposed to participate in immune functions.This laboratory has focused on lectins as 'non-self' recognition molecules, as the first step of the immune response in invertebrates, using the protochordate Clavelina picta as the model organism. Protochordates lack adaptive immunity, and thus, are suitable models to examine innate immunity mechanisms of invertebrates that may have been conserved through the vertebrate lineages. With prior NSF support this laboratory has: (a) identified and characterized in C. picta a unique soluble C-type lectin (CPL-III) that not only carries both MBL- and selectin-like CRDs, in a single polypeptide subunit, but also binds both 'non-self' (environmental bacteria) and 'self' (tunic sulfated glycan) ligands, (b) achieved partial characterization of putative molecular partners for complement activation, the serine protease MASP, and complement component C3, (c) demonstrated the presence of a CPL-III-like protein on the surface of the hemocytes, and (d) characterized two distinct galectins, one of which is distinctly expressed in hemocytes. By addressing the structure and functional aspects of CPL-III, MASP, C3, and galectin, and investigating their coordinated activity, this research will establish a link between C-type lectins and galectins in complement activation and opsonization. Preliminary results make C. picta an ideal model system to examine the potential coordinate expression and biological roles of the two lectin classes (C-type lectins and galectins) in innate immunity. The tandem organization of CPL-III distinct CRDs, their homologies to mammalian MBL and selectins, and their binding to 'self' and 'non-self' carbohydrate ligands, may provide insight into the evolutionary history of mammalian collectins and selectins. Furthermore, to establish the role of CPL-III as the 'trigger' of an integrally functional lectin-mediated complement activation pathway, would constitute the strongest indication that this pathway preceded the antibody-mediated pathway in evolution, as proposed earlier upon the discovery of C3 in deuterostome invertebrates. This would represent a fundamental advance in our understanding of innate immunity, which would transcend the invertebrates/vertebrates boundary.