Figure 9.

Innate receptor activation pattern resulting from a coinfection of the Influenza A virus and Haemophilus influenzae (as often occurred during the Great Influenza Pandemic of 1918–1919) [22,23]. Note the differences from Figure 3A and Figure 8 (severe COVID-19 patients). Note also that there is an antagonistic effect of NOD2 activation on RIG1 and TLR9, an antagonism of TLR7 for TLR9 and an antagonism of TLR4 on TLR8 that may explain the absence of RIG1, TLR8 and TLR9 activation in influenza-associated ALI/ARDS (Table 1), despite the activation of RIG1, TLR8 and TLR9 by the influenza A virus (Table 2). It seems likely that other RIG1 and TLR8 antagonisms (e.g., from NOD1) also exist that are yet to be described. For other TLR, the number of synergisms outnumber the antagonisms, so these receptors will presumably continue to be activated.