Different Staphylococcus aureus whole bacteria mutated in putative pro-inflammatory membrane components have similar cytokine inducing activity

The role of the different major cell wall components of Gram-positive bacteria for immune stimulation is controversial. We thus compared the cytokine inducing capacity of different Staphylococcus aureus (SA) mutants lacking either lipoproteins (SA 113 Δlgt), or wall teichoic acids (WTA) (ΔTA), or possessing a reduced d-alanine content in lipoteichoic acid (LTA) (SA 113 Δdlt) to its corresponding wildtype (SA 113 wt). Inactivated whole bacteria and their purified cell wall components peptidoglycan and LTA, were used to stimulate human whole blood and macrophages from TLR2 knock-out mice. We found that all S. aureus strains induced similar amounts of TNF, IL-8 and IL-10 and none of them was dependent on the presence of TLR2. Surprisingly, in case of SA 113 Δlgt a significant attenuated release of only IL-1β protein and mRNA in human whole blood was observed. Highly purified peptidoglycan from all strains in contrast to LTA had a very low activity in stimulating cytokine release. Taken together these results demonstrate that major cell wall alterations like lack of WTA, lipoproteins or alterations in d-alanine content do not affect the overall cytokine inducing potential of whole bacteria and thus cytokine induction is initiated by redundant mechanisms.