Activation of the Alternative Complement Pathway by Pneumococcal Cell Wall Teichoic Acid

Abstract Previous studies have shown that the cell wall plays a major role in the activation of the alternative pathway by the pneumococcus. The present studies were performed in order to identify the biochemical component of the pneumococcal cell wall responsible for activating the alternative pathway. Teichoic acids were extracted from purified pneumococcal cell walls by three different procedures, and in each case they were able to activate the alternative pathway at concentrations as low as 3 to 10 µg/ml. In contrast, the residual cell walls, which contained the peptidoglycan, lost their activity in proportion to the amount of teichoic acid that had been extracted. Notably, cell walls extracted with periodate lost over 98% of their teichoic acid and the residual peptidoglycan was unable to activate the alternative pathway at concentrations as high as 1 mg/ml. When an autolysin defective pneumococcal strain is grown in the presence of penicillin, cell wall polymers are secreted into the medium. Crude preparations of secreted cell wall polymers were found to be able to activate the alternative pathway. The activity was removed by absorption with TEPC-15 myeloma with anti-choline specificity. Since both cell wall teichoic acid and lipoteichoic acid contain choline and are removed by TEPC-15 absorption, the activity in the crude preparations of cell wall polymers could have been due to one or both of these compounds. However, purified lipoteichoic acid was unable to activate the alternative pathway. Thus, the ability of crude preparations of cell wall polymers to activate the alternative pathway was due to the presence of cell wall teichoic acid. The results of these studies demonstrate that cell wall teichoic acid, rather than peptidoglycan, is responsible for pneumococcal activation of the alternative pathway.