Serum IgM and C-Reactive Protein Binding to Phosphorylcholine of Nontypeable Haemophilus influenzae Increases Complement-Mediated Killing.

Abstract

Nontypeable Haemophilus influenzae (NTHi) colonizes the human upper respiratory tract without causing disease symptoms, but it is also a major cause of upper and lower respiratory tract infections in children and elderly, respectively. NTHi synthesizes various molecules to decorate its lipooligosaccharide (LOS), which modulates the level of virulence. The presence of phosphorylcholine (PCho) on NTHi LOS increases adhesion to epithelial cells, which is an advantage for the bacterium enabling nasopharyngeal colonization. However, when PCho is incorporated on the LOS of NTHi, it is recognized by the acute-phase C-reactive protein (CRP) and PCho-specific antibodies, both potent initiators of the classical pathway of complement activation. We determined the presence of PCho and binding of IgG and IgM to the bacterial surface for 319 NTHi strains collected from the nasopharynx/oropharynx, middle ear, and lower respiratory tract. PCho detection was higher for NTHi strains collected from the nasopharynx/oropharynx, which was associated with increased binding of IgM and IgG to the bacterial surface. Binding of CRP and IgM to the bacterial surface of PChohigh NTHi strains increased complement-mediated killing, which was largely dependent on PCho-specific IgM. The levels of PCho-specific IgM varied in sera from 12 healthy individuals, and higher PCho-specific IgM levels were associated with increased complement-mediated killing of a PChohigh NTHi strain. In conclusion, incorporation of PCho on the LOS of NTHi marks the bacterium for binding of CRP and IgM, resulting in complement-mediated killing. Therefore, having a lower PCho might be beneficial in situations where sufficient PCho-specific antibodies and complement are present.