Gonococci possessing only certain P.II outer membrane proteins interact with human neutrophils

Abstract

We investigated the role of the protein II (P.11) family of gonococcal outer membrane proteins in the interaction of seven single P.11 variants of Neisseria gonorrhoeae FA1090 with human neutrophils in vitro. The abilities of nonpiliated gonococci to adhere to and be killed by neutrophils and to stimulate luminol-dependent chemiluminescence (CL) depended on the possession of at least one P.11. Gonococci lacking P.11 (i.e., P.II-) adhered poorly to and were not killed by neutrophils and induced only minimal CL. Although most P.11-containing (i.e., P.II+) variants adhered to, stimulated, and were readily killed by neutrophils, one variant, containing P.IIa, possessed none of these characteristics; it acted just like a P.IIvariant. No correlation was found between the colony opacity phenotype and the interaction of gonococci with neutrophils. Data from CL experiments suggest that the stimulatory effect of P.II was dominant over that of pili; i.e., piliated P.II+ gonococci were much more stimulatory than piliated P.IIgonococci. The results indicate that most but not all P.11 proteins mediate, in part or in full, the interaction of N. gonorrhoeae with human neutrophils, including adherence, stimulation of the neutrophil respiratory burst, and phagocytic killing.

Retinoic acid treated HL60 cells express CEACAM1 (CD66a) and phagocytoseNeisseria gonorrhoeae

“…This increased association of Opa þ gonococci with human neutrophils was first observed by [3,4]. Subsequently, several other groups demonstrated that Opa proteins mediated interaction to neutrophils in an opsonin-independent manner [5][6][7].…”

“…If CEACAM1 is participating in the interaction of gonococci with neutrophils, the neutrophils should also phagocytose the Opa À gonococci. But, it is well-known that neutrophils mainly phagocytose Opa þ gonococci but not Opa À gonococci [4,7,22,[29][30][31]. Our explanation is that CEACAM1 is an inhibitory receptor that contains an immunoreceptor tyrosine-based inhibition motif (ITIM) [32].…”

Neisseria gonorrhoeaesuppresses the oxidative burst of human polymorphonuclear leukocytes

“…In the absence of Opa expression, Gc fail to stimulate a sizable PMN oxidative burst, but the strains tested in these studies also lacked adhesins (e.g. type IV pili) that could potentially facilitate Opa-independent interactions with PMNs (Rest et al, 1982;Virji and Heckels, 1986;Fischer and Rest, 1988;Elkins and Rest, 1990). In re-examining the data in these reports, Opa -Gc do appear to trigger some degree of ROS production from PMNs, albeit less than their Opa + counterparts (Rest et al, 1982;Virji and Heckels, 1986).…”

“…ROS production was measured in PMNs that were left uninfected, or infected with moi 260 of liquid-grown OpaB + Gc that were live or had been killed by heating (HK). Heckels, 1986;Fischer and Rest, 1988;Naids and Rest, 1991;Gray-Owen et al, 1997;Simons et al, 2005). When FA1090 OpaB + Gc were harvested from agar plates and presented to PMNs, they elicited eightfold more total LDCL from PMNs than liquid-grown Gc, even though the viable cfu present in the liquid-grown culture outnumbered the plate-grown by a factor of 10 ( Fig.…”

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.…”