The L412F Variant of Toll-Like Receptor 3 Is Associated with Cutaneous Candidiasis, Increased Susceptibility to Cytomegalovirus, and Autoimmunity

The study examined the L412F variant of Toll-like receptor 3 (TLR3) in 21 patients with chronic mucocutaneous candidiasis (CMCC) who did not have mutations in other known genes linked to the condition. It was found that 66% of these patients carried the L412F variant, which was associated with a higher incidence of severe viral infections, especially cytomegalovirus (CMV), and autoimmune disorders. The variant impaired TLR3 function, resulting in reduced activation of NF-κB and decreased secretion of IFN-γ, both essential for proper immune responses. The study suggested that the L412F variant played a role in the clinical symptoms observed in these patients, including frequent severe infections and immune system irregularities.