The Battle Between Influenza and the Innate Immune Response in the Human Respiratory Tract

Nicholls, John M

TLPR 2 and 4 are present on the cell surface and recognize viral surface glycoproteins, while TLR 3 and 7 are present intracellularly and recognized double stranded viral RNA (dsRNA) and single stranded RNA viral RNA9(ssRNA) respectively. Shinya and colleagues previously demonstrated that prestimulation of TLR2 and 4 had a protective effect in mice when challenged with HPAI and that this protective effect was also seen after pre-treatment with lipopolysaccharide (LPS) which is a ligand for TLR4 [55] . This TLR4 binding resulted in the activation of 2 independent pathways -one involving MyD88 and the other TRIF. This pathway also required 2 surface molecules MDM2 and CD14, and additional studies demonstrated that cultures lacking either MD2 or CD14 had no change in H5N1 replication after LPS stimulation [56] . Interestingly, while LPS alone did not affect the expression of interferon stimulation genes. It did lead to an upregulation of the expression of other antiviral molecules, and TLR3 was found to be upregulated in this TLR4-TRIF pathway, thus demonstrating that the suppression of H5N1 infection was aided by the synergistic upregulation of TLR3. This finding is of interest because TLR3 was previously thought to recognize only dsRNA [57] .