HMGB1 is a damage-associated molecular pattern (DAMP) secreted during immune cell activation or cell death (Fig. 2).53,54 By binding to TLR4 and receptor for advanced glycation endproducts (RAGE) receptors, HMGB1 can contribute to inflammation and inhibition of HMGB1 has been experimentally investigated as treatment for sepsis and cerebral ischaemia.55-57 Two studies have evaluated inhibition of HMGB1 as strategy for adjunctive therapy in pneumococcal meningitis.58,59. Here, TLR4 is linked to pneumococcal meningitis.