My laboratory is interested in innate immune responses modulated by plasma proteins and expression of antimicrobial peptides regulated by signal transduction pathways in a model insect, the tobacco hornworm Manduca sexta. Insects lack an immunoglobulin-mediated acquired immunity, but they have developed an effective and sophisticated immune system similar to the innate immune system of vertebrates. In the innate immune system, recognition of pathogens and differentiation of nonself are critical to the host animals to trigger effective immune responses. Initial recognition of pathogens in innate immunity is mediated by pattern recognition receptors (PRRs) that can recognize structural molecular patterns, termed pathogen-associated molecular patterns (PAMPs), present on the surface of many microbes and pathogens but not on the host cells. Our research focuses on:
- C-type lectins as key PRRs in innate immune responses. C-type lectins are calcium-dependent carbohydrate-binding proteins. We have discovered a group of at least four C-type lectins, named immulectins, in M. sexta. These immulectins can enhance hemocyte (blood cell) phagocytosis, encapsulation and melanization. Our current work is to investigate how immulectins recognize and bind to microbial surface molecules such as bacterial lipopolysaccharide (LPS) and lipoteichoic acid (LTA), to trigger innate immune responses.
- Modulation of phenoloxidase (PO) activation. Melanotic encapsulation is an effective immune response to pathogens, particularly to large pathogens like nematodes and parasitoid eggs. Melanization requires activation of PO, a process that involves a cascade of serine proteinases. However, PO activation can also be modulated by non-enzymatic proteins. For example, we found that serine proteinase homologs (SPHs) are essential co-factors in PO activation by proteinases. We also found that a small cationic protein, lysozymes, and immulectins can either positively or negatively regulate PO activity. Currently, we are investigating how these proteins can modulate PO activation.
- Regulation of antimicrobial peptide genes. Insects can synthesize a variety of antimicrobial peptides (AMPs) upon microbial infections. The majority of AMPs is present in all insects, while some are species-specific. For example, Gloverin and Moricin are found only in Lepidoptera but not in Diptera (Drosophila and mosquitoes). Expression of AMPs is regulated by signal transduction pathways, such as the Toll and IMD (immune deficiency) pathways in Drosophila. Our research is to investigate how AMPs, particularly Gloverin and Moricin, are regulated in M. sexta hemocytes, and to identify additional signaling pathways that may activate AMPs by LPS.
Chowdhury M, Li CF, He Z, Lu Y, Liu XS, Wang YF, Ip YT, Strand MR, Yu XQ. Toll family members bind multiple Spätzle proteins and activate antimicrobial peptide gene expression in Drosophila. (2019). The Journal of biological chemistry, Journal Article.
Deng J, Yu XQ, Wang PH. Inflammasome activation and Th17 responses. (2019). Molecular immunology, 107 142-164. Journal Article, Review.
Chowdhury M, Zhang J, Xu XX, He Z, Lu Y, Liu XS, Wang YF, Yu XQ. An in vitro study of NF-κB factors cooperatively in regulation of Drosophila melanogaster antimicrobial peptide genes. (2019). Developmental and comparative immunology, 95 50-58. Journal Article.