TLR4 and Immunodeficiency: In the pioneering studies on Drosophila melanogaster it was found that the immune deficiency (IMD) pathway regulated immune responses to Gram-negative (Gr−) bacteria, the Toll pathway regulated responses to fungi and Gram-positive (Gr+) bacteria, and the Janus kinase-signal transducer and activator of transcription and RNA interference pathways regulated responses to bacteria, viruses, and parasitoids [17–22].