Figure 2.
A comparison of the mammalian complement system and the lepidopteran complement-like system.(A) The mammalian complement system consists of three pathways that have overlapping components and functions. The classical pathway begins with antibody recognition of an antigen on the foreign organism's surface, and the subsequent binding of the C1 complex to the antibodies. In the lectin pathway, mannose binding lectin (MBL) along with mannan-binding lectin serine protease 2 (MASP2) binds to a carbohydrate on the foreign organism. Both the C1 and MBL/MASP complexes hydrolyze C2 and C4. C4b and C2a fragments form a C3 convertase that hydrolyzes C3 into C3b fragments, which binds to foreign surfaces and acts as an opsonin—a compound that promotes phagocytosis. In the alternative pathway, C3 spontaneously hydrolyzes into C3b in plasma, which binds Factor B to form C3bB and is further hydrolyzed by Factor D to form C3bBb, a C3 convertase. Both C3 convertases bind to C3b to form a C5 convertase that hydrolyzes C5. C5b binds C6–9 and forms a membrane attack complex (MAC) that forms a pore in the microbe's cell membrane leading to lysis. (B) Although the G. mellonella complement-like system is unstudied, the complement-like system of other Lepidoptera is partially known. In B. mori and M. sexta, thioester-containing proteins (TEPs) are hypothesized to play C3-like roles. In mosquitoes (inset, yellow), TEP1 is well studied and plays a C3-like role. TEP1 is likely hydrolyzed in hemolymph, and brought to the surface of a pathogen by the leucine-rich repeat proteins (LRRs) LRIM-1 and APL-1, while it is unknown whether LRRs play similar roles in Lepidoptera. TEP proteins may opsonize similar to C3b in mammals. A TEP-convertase that hydrolyzes more TEPs is not known in Lepidoptera; however, a TEP1-convertase in mosquitoes consists of hydrolyzed TEP1 and a serine protease homolog (SPH) SPCLIP1, which activates other serine proteases (CLIPA8). In Lepidoptera, protease activation may occur downstream of TEP deposition, leading to phenoloxidase-activating proteases (PAPs) activation, which then activate phenoloxidases (PO) and SPH. PO and SPH form complexes known as melanization complexes (MCs) that lead to melanization, lysis and oxidative stress at the surface of foreign organisms.