Streptococcus pneumoniae interactions with the complement system

Abstract

Host innate and adaptive immunity to infection withStreptococcus pneumoniaeis critically dependent on the complement system, demonstrated by the high incidence of invasiveS. pneumoniaeinfection in people with inherited deficiency of complement components. The complement system is activated byS. pneumoniaethrough multiple mechanisms. The classical complement pathway is activated by recognition ofS. pneumoniaeby C-reactive protein, serum amyloid P, C1q, SIGN-R1, or natural or acquired antibody. SomeS. pneumoniaestrains are also recognised by ficolins to activate the mannose binding lectin (MBL) activation pathway. Complement activation is then amplified by the alternative complement pathway, which can also be activated byS. pneumoniaedirectly. Complement activation results in covalent linkage of the opsonic complement factors C3b and iC3b to theS. pneumoniaesurface which promote phagocytic clearance, along with complement-mediated immune adherence to erythrocytes, thereby protecting against septicaemia. The role of complement for mucosal immunity toS. pneumoniaeis less clear. Given the major role of complement in controlling infection withS. pneumoniae, it is perhaps unsurprising thatS. pneumoniaehas evolved multiple mechanisms of complement evasion, including the capsule, multiple surface proteins, and the toxin pneumolysin. There is considerable variation betweenS. pneumoniaecapsular serotypes and genotypes with regards to sensitivity to complement which correlates with ability to cause invasive infections. However, at present we only have a limited understanding of the main mechanisms causing variations in complement sensitivity betweenS. pneumoniaestrains and to non-pathogenic streptococci.