In a mouse model system, a gene mutation in a toll-like receptor (TLR) increases susceptibility to adenovirus infection. Which TLR is affected?

The correct answer is TLR9 because it is specifically involved in recognizing viral DNA, particularly from DNA viruses like adenovirus. Toll-like receptors (TLRs) play a critical role in the innate immune system by recognizing pathogen-associated molecular patterns. TLR9 is located in endosomal compartments and is activated by unmethylated CpG motifs found in viral DNA, which are common in adenoviruses.

A mutation in TLR9 that impairs its function could lead to a decreased ability to detect and mount an immune response against adenovirus, resulting in increased susceptibility to infection. Other TLRs, such as TLR2, TLR4, and TLR6, are primarily associated with the recognition of bacterial components and do not have the same direct involvement in sensing viral infections like TLR9 does. Therefore, the increased susceptibility to adenovirus in the context of a mutation in a TLR indicates that TLR9 is the affected receptor.