Differential influences of complement on neutrophil responses to Neisseria meningitidis infection

• Published in: Pathogens and disease Vol. 76; no. 8
• Main Authors: Krüger, Sören, Eichler, Emma, Strobel, Lea, Schubert-Unkmeir, Alexandra, Johswich, Kay O
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01-11-2018
• Subjects: Antisera; Blood; Bursting strength; Cell activation; Cerebrospinal fluid; Complement; Complement activation; Complement component C3; Degranulation; Interleukin 8; Leukocytes (neutrophilic); Meningitis; Neisseria meningitidis; Neutrophils; Phagocytes
• ISSN: 2049-632X; 2049-632X
• DOI: 10.1093/femspd/fty086

The complement system is the primary innate immune determinant protecting against invasive diseases caused by the Gram-negative bacterium Neisseria meningitidis (Nme, meningococcus), as evidenced by the extreme susceptibility of individuals with complement deficiencies. In contrast, the role of phagocytes such as neutrophils is much less well understood, although they are recruited in great numbers to the cerebrospinal fluid during meningococcal meningitis. Here, we consider the interaction of Nme with primary human neutrophils using either purified cells or a whole blood model of infection. We found that neutrophils are capable of non-opsonic uptake and killing of different Nme strains. However, in the presence of immune serum featuring active complement, Nme association is strongly increased, whereas this is not the case in heat-inactivated immune serum. Blockade of complement at the level of C3 using the inhibitor compstatin Cp20 reduces the uptake dramatically. In addition, purified neutrophils did not mount an oxidative burst towards Nme unless complement was added and, vice versa, the oxidative burst was strongly reduced in whole blood upon complement inhibition. In contrast, there was no significant impact of complement on neutrophil degranulation or IL-8 secretion. Taken together, neutrophils require complement activation in order to mount a full response towards Nme.