Current Genome-Wide Analysis on Serine Proteases in Innate Immunity

Jeak   L   Ding; Lihui      Wang; Bow      Ho

Abstract

Recent studies on host defense against microbial pathogens have demonstrated that innate immunity predated adaptive immune response. Present in all multicellular organisms, the innate defense uses genome-encoded receptors, to distinguish self from non-self. The invertebrate innate immune system employs several mechanisms to recognize and eliminate pathogens: (i) blood coagulation to immobilize the invading microbes, (ii) lectin-induced complement pathway to lyse and opsonize the pathogen, (iii) melanization to oxidatively kill invading microorganisms and (iv) prompt synthesis of potent effectors, such as antimicrobial peptides. Serine proteases play significant roles in these mechanisms, although studies on their functions remain fragmentary, and only several members have been characterized, for example, the serine protease cascade in Drosophila dorsoventral patterning; the Limulus blood clotting cascade; and the silk worm prophenoloxidase cascade. Additionally, serine proteases are involved in processing Späetzle, the Toll ligand for signaling in antimicrobial peptide synthesis. The recent completion of the Drosophila and Anopheles genomes offers a tantalizing promise for genomic analysis of innate immunity of invertebrates. In this review, we discuss the latest genome-wide studies conducted in invertebrates with emphasis on serine proteases involved in innate immune response. We seek to clarify the analysis by using empirical research data on these proteases via classical approaches in biochemical, molecular and genetic methods. We provide an update on the serine protease cascades in various invertebrates and map a relationship between their involvement in early embryonic development, blood coagulation and innate immune defense.

Keywords: serine proteases, proteolytic cascades, innate immunity, genomics, dna microarray, empirical approaches

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