Opa proteins and CEACAMs: pathways of immune engagement for pathogenicNeisseria

Abstract

Neisseria meningitidis and Neisseria gonorrhoeae are globally important pathogens, which in part owe their success to their ability to successfully evade human immune responses over long periods. The phase-variable opacity-associated (Opa) adhesin proteins are a major surface component of these organisms, and are responsible for bacterial adherence and entry into host cells and interactions with the immune system. Most immune interactions are mediated via binding to members of the carcinoembryonic antigen cell adhesion molecule (CEACAM) family. These Opa variants are able to bind to different receptors of the CEACAM family on epithelial cells, neutrophils, and T and B lymphocytes, influencing the innate and adaptive immune responses. Increased epithelial cell adhesion creates the potential for prolonged infection, invasion and dissemination. Furthermore, Opa proteins may inhibit T-lymphocyte activation and proliferation, B-cell antibody production, and innate inflammatory responses by infected epithelia, in addition to conferring increased resistance to antibody-dependent, complement-mediated killing. While vaccines containing Opa proteins could induce adhesion-blocking and bactericidal antibodies, the consequence of CEACAM binding by a candidate Opa-containing vaccine requires further investigation. This review summarizes current knowledge of the immunological consequences of the interaction between meningococcal and gonococcal Opa proteins and human CEACAMs, considering the implications for pathogenesis and vaccine development.

Neisseria meningitidis NalP cleaves human complement C3, facilitating degradation of C3b and survival in human serum

“…S5). The species specificity of NalP is consistent with the other Nm proteins that interact specifically with human factors, which include fHbp, NspA, opacity proteins, and transferring binding protein (13,24,31,32). The specificity of interactions with human factors may explain why Nm is strictly a human pathogen and why antibody-mediated killing of Nm in vitro is more efficient when complement is derived from rabbits, rats, or mice, with fH and C3 that are not recognized by fHbp, NspA, or NalP, respectively.…”

Seminal Plasma Promotes Neisseria gonorrhoeae Aggregation and Biofilm Formation

“…The Opa family of proteins is a group of major N. gonorrhoeae adhesins that interact principally with carcinoembryonic antigen cell adhesion molecule family proteins on the surface of host cells (33). The Opa proteins are also known to facilitate gonococcal aggregation (34); as such, the influence of Opa proteins on SPmediated loss of adherence was tested.…”

Fur-Mediated Global Regulatory Circuits in Pathogenic Neisseria Species

“…Gonococcal Opa proteins have been shown to be expressed during natural infections as well as in experimentally infected volunteers (54,55,93). Furthermore, Opa-carcinoembryonic antigen-related cell adhesion molecule (CEACAM) interactions have been shown to promote gonococcal colonization in mouse models (16,75,76,82). Above all, these results suggest that specific colonization niches and the associated pathogenic processes of the two pathogenic species serve to define the Fur regulons of these organisms and, in particular, those genes which are activated by Fur.…”