Figure 10.

Activation pattern model for polymicrobial sepsis based on a combination of Gram-positive and Gram-negative bacteria from Table 2. Note the several antagonistic interactions on TLR8, which may explain why it is not activated during sepsis. TLR1 is also antagonized (in this case, by NOD2 and, probably, NOD1 as well) and has no synergisms to offset these, so it, too, does not appear to be activated during sepsis (Table 1 and Table 5). For other TLR, synergisms outnumber the antagonisms, so these receptors will presumably continue to be activated with TLR8-activating PAMPs (Table 1 and Table 5). A very similar pattern results from combinations of bacteria with fungi, as can be seen with reference to Table 2 and Table 3. Note the distinct differences from Figure 3A and Figure 8 (severe COVID-19) and Figure 3B and Figure 9 (influenza-associated ALI/ARDS), illustrating the fact that cytokine storms may have distinctly different patterns of innate receptor activation.