Complement activation on Chlamydia pneumoniae is accelerated by direct binding of native properdin to its surface (37.10)

Abstract

Abstract Activation of complement represents one means of natural resistance to infection from a wide variety of potential pathogens. Recently properdin, a positive regulator of the alternative pathway of complement, has been shown to bind to surfaces and activate complement de novo. Here we studied the molecular mechanisms of properdin-mediated complement activation on Chlamydia pneumoniae, an obligate intracellular gram-negative bacterium that causes upper respiratory tract infections. We analyzed the ability of properdin to initiate complement activation by binding to C. pneumoniae directly, providing a platform for de novo convertase assembly. We determined for the first time that the physiological P2-P4 forms of human properdin bind to the surface of C. pneumoniae. The binding of these physiological forms initiates and accelerates complement activation on the C. pneumoniae surface, as measured by C3b and C9 deposition. Finally, properdin-depleted serum could not control C. pneumoniae infection of HEp-2 cells when compared with normal human serum. However, addition of native properdin to properdin depleted serum recovered the ability of serum to control the infection. Altogether, our data suggest that properdin is a pattern recognition molecule that plays a role in resistance to Chlamydia infection.