Serine proteases as mediators of mosquito immune responses

Serine proteases regulate several invertebrate defense responses, including hemolymph coagulation, antimicrobial peptide synthesis, and melanization o f pathogen surfaces. These processes require the presence of serine proteas es in the hemolymph where they can rapidly activate immune pathways in resp onse to pathogen detection. Hemolymph coagulation in the horseshoe crab is controlled by several serine proteases, including two that are pathogen rec ognition molecules and two in the clip domain family of serine proteases. T he antimicrobial peptide synthesis and melanization pathways include clip d omain proteases as well as other, uncharacterized serine proteases. We have identified five serine proteases from the hemolymph of the mosquito, Anoph eles gambiae. One, Sp22D, is a large protease with potential pathogen bindi ng domains. Sp22D is expressed in three tissues that have immune functions (midgut epithelium, fat body, and hemocytes), and its transcript abundance increases after immune challenge. Sp14A, Sp14D1, and Sp14D2 are clip domain serine proteases that are similar to enzymes with presumed roles in melani zation or antimicrobial peptide synthesis. They undergo changes in transcri pt abundance in response to infection with bacteria or malaria parasites, a nd they reside in a chromosomal region that has been associated with melani zation of parasites. Sp18D, also a clip domain protease, is similar to a Ma nduca protease with a likely role in immunity, but immune challenge does no t affect its mRNA abundance. (C) 2001 Elsevier Science Ltd. All rights rese rved.