Nonopsonic Phagocytosis of Group C Neisseria meningitidis by Human Neutrophils

Abstract

Although complement-mediated bactericidal activity in serum has long been known to be very important in host defense againstNeisseria meningitidis, recent studies have shown that opsonic phagocytosis by neutrophils is also important. The purpose of this study was to determine if endemic group C N. meningitidis strains were susceptible to nonopsonic (complement- and antibody-independent) phagocytosis by human neutrophils, which is a well-described phenomenon for Neisseria gonorrhoeae. Gonococci that possess one or more of a group of heat-modifiable outer membrane proteins (called opacity-associated [Opa] proteins) are phagocytosed by neutrophils in the absence of serum. We found that four serogroup C meningococcal strains bearing the lacto-N-neotetraose (LNnT) structure on lipooligosaccharide (LOS) were phagocytosed by neutrophils in the absence of antibody and active complement. Confocal microscopy confirmed that the organisms were internalized by neutrophils. This susceptibility was not restricted to carrier isolates, since two of the strains were cultured from blood or cerebrospinal fluid. All four strains expressed Opa protein and had relatively less endogenous LOS and capsule sialylation compared to six strains that were resistant to this type of phagocytosis. Nonopsonic phagocytosis of two of the four strains was inhibited by exogenous sialylation of LOS LNnT and the binding of monoclonal antibody to LNnT. However, an isogenic mutant that lacked the LNnT structure was fully susceptible to nonopsonic phagocytosis. We conclude that group C meningococci can be phagocytosed by neutrophils in the absence of antibody and active complement possibly by two different mechanisms. Expression of Opa protein and downregulation of endogenous surface sialic acids analogous to what is seen for N. gonorrhoeae might be necessary for N. meningitidis as well.

Mannose-binding lectin enhances phagocytosis and killing ofNeisseria meningitidisby human macrophages

“…It is known that pathogenic Neisseria have a number of mechanisms for adhering or modifying binding to host cells in the absence of "opsonization" [30,31] including Rho GTPasedependent and -independent pathways mediated by gonococcal opa [32]. Our results would be consistent with a Rho-independent mechanism being present for Neisseria, as a low level of bacterial uptake still occurred in the presence of toxin B, which inhibits Rho GTPase activity.…”

Imatinib inhibits the functional capacity of cultured human monocytes

“…16,17 In the absence of opsonization, foreign particles are phagocytosed by means of lectinophagocytosis, whereby the particle interacts with mannan and β-glucan receptors on the surface of the macrophage. [17][18][19] We wished to determine whether imatinib impaired the ability of macrophages to phagocytose non-opsonized and opsonized zymosan particles that consist of mannan and β-glucan. Opsonin-independent phagocytosis by M-CM was most susceptible to imatinib treatment (1.0 µmol/L), while the number of M-CM undergoing opsonin-dependent phagocytosis and GM-CM undergoing opsonin-dependent and -independent phagocytosis was affected at higher concentrations of imatinib (5.0 µmol/L).…”

Opa proteins and CEACAMs: pathways of immune engagement for pathogenicNeisseria

“…The majority of Opa-expressing Neisseria interact with neutrophils, hence their original name of leucocyte association proteins (Swanson et al, 1975). Opa mediates intimate attachment of Neisseria to neutrophils, as well as subsequent nonopsonic phagocytosis and stimulation of the bactericidal oxidative burst response (King & Swanson, 1978;Virji & Heckels, 1986;Fischer & Rest, 1988;Elkins & Rest, 1990;Belland et al, 1992;Chen & Gotschlich, 1996;Gray-Owen et al, 1997a, b;McNeil & Virji, 1997;Estabrook et al, 1998;Sarantis & Gray-Owen, 2007). Phagocytosis by and stimulation of neutrophils would seem to confer a selective disadvantage to Opa-expressing bacteria, which would be killed by the bactericidal response.…”