The mechanism of neutropenia, TLR8-GOF’s key feature, appears multifactorial with the aspects of both production and destruction mechanisms, based on antineutrophil antibodies, direct cytotoxicity and/or the Fas ligand–mediated destruction of neutrophils and progenitor cells, and impaired neutrophil differentiation and survival through pro-inflammatory mediators. This evidence concerns the gene TLR8 and Decreased total neutrophil count.