Drice negatively regulates cellular and humoral immunity of Drosophila melanogaster

The innate immune response is a double-edged sword in insects, comprising the humoral and cellular mechanisms to fight and eliminate pathogens. The humoral response is achieved by the production of antimicrobial peptides, which are secreted in the hemolymph. The cellular responses are mediated by phagocytosis, encapsulation and melanization. Though the fat bodies are the primary immune tissues in Drosophila, secreting AMPs, the Malpighian tubules are also autonomous immune organs that constitutively secrete AMPs at basal levels, which increases after infection. Here we provide evidence to show that the caspase 3 homolog in Drosophila, Drice, negatively regulates both, cellular as well as humoral immunity. Depletion of Drice leads to the increased expression of transcription factor Relish, which enhances the expression of certain AMPs regulated by the IMD pathway. In the absence of Drice, both the Ecdysone receptor- B1 and Broad-core (Br-C) are also upregulated which are upstream regulators of the IMD pathway. The increase in crystal cells clearly indicates Drice to be a negative regulator of this form of cellular immunity. Collectively our findings suggest the role of Drice in the immune regulation of Drosophila melanogaster, and these results will add to the growing understanding of diverse roles of caspases in immune regulation.