TLR9: A friend or a foe

The innate immune system is a primary protective line in our body. It confers its protection through different pattern recognition receptors (PRRs), especially toll like receptors (TLRs). Toll like receptor 9 (TLR9) is an intracellular TLR, expressed in different immunological and non-immunological cells. Release of cellular components, such as proteins, nucleotides, and DNA confers a beneficial inflammatory response and maintains homeostasis for removing cellular debris during normal physiological conditions. However, during pathological cellular damage and stress signals, engagement between mtDNA and TLR9 acts as an alarm for starting inflammatory and autoimmune disorders. The controversial role of TLR9 in different diseases baffled scientists if it has a protective or deleterious effect after activation during insults. Targeting the immune system, especially the TLR9 needs further investigation to provide a therapeutic strategy to control inflammation and autoimmune disorders.