For a study, researchers sought to investigate the link between TLR3 L412F and AE-related death in IPF patients. They sought to determine how TLR3 L412F polymorphism affected the lung microbiota and antibacterial TLR responses in primary lung fibroblasts from IPF patients. TLR-mediated antibacterial and antiviral responses were measured by ELISA, Western blot analysis, and quantitative PCR in L412F wild-type and 412F-heterozygous direct lung fibroblasts from IPF patients. In nasopharyngeal lavage samples from patients with AE-IPF, hierarchical heatmap analysis was used to determine bacterial and viral grouping. The effect of TLR3 L412F on the IPF lung microbiota was studied using 16S ribosomal RNA quantitative PCR and pyrosequencing. A substantial increase in AE-related fatality was found in patients with 412F-variant IPF. Antibacterial TLR responses to LPS (TLR4), Pam3CYSK4 (TLR1/2), flagellin (TLR5), and FSL-1 (TLR6/1) were shown to be diminished in 412F-heterozygous IPF lung fibroblasts, as well as responses to live Pseudomonas aeruginosa infection. Investigators showed that 412F-heterozygous individuals with IPF have a dysregulated lung microbiome with higher frequencies of Streptococcus and Staphylococcus spp. Using 16S ribosomal RNA sequencing. TLR3 L412F dysregulated the IPF lung microbiome and decreases the responses of IPF lung fibroblasts to bacterial TLR agonists and live bacterial infection, according to the research. The outcomes suggested that TLR3 L412F might play a role in AE mortality caused by viruses and bacteria.