Increased translocation of Gram-negative bacteria with increased LPS load is probably a major trigger factor, but also other bacterial infections, toxoplasmosis, viral infections (e.g., cytomegalovirus), cancer, and gastrointestinal, autoimmune, immune-inflammatory, neuroinflammatory, and neurodegenerative disorders appear to be associated with those pathways via activation of TLR/LTF/TWEAK signaling. This evidence concerns the gene TNFSF12 and bacterial infectious disease.