Mutans Streptococcal Infection Induces Salivary Antibody to Virulence Proteins and Associated Functional Domains

Abstract

The interplay between mucosal immune responses to natural exposure to mutans streptococci and the incorporation and accumulation of these cariogenic microorganisms in oral biofilms is unclear. An initial approach to explore this question would be to assess the native secretory immunity emerging as a consequence of Streptococcus mutans infection. To this end, we analyzed salivary immunoglobulin A (IgA) antibody to mutans streptococcal glucosyltransferase (Gtf) and glucan binding protein B (GbpB) and to domains associated with enzyme function and major histocompatibility complex (MHC) class II binding in two experiments. Salivas were collected from approximately 45-day-old Sprague-Dawley rats, which were then infected with S. mutans SJ32. Infection was verified and allowed to continue for 2 to 2.5 months. Salivas were again collected following the infection period. Pre-and postinfection salivas were then analyzed for IgA antibody activity using peptide-or protein-coated microsphere Luminex technology. S. mutans infection induced significant levels of salivary IgA antibody to Gtf (P < 0.002) and GbpB (P < 0.001) in both experiments, although the levels were usually far lower than the levels achieved when mucosal immunization is used. Significantly (P < 0.035 to P < 0.001) elevated levels of postinfection salivary IgA antibody to 6/10 Gtf peptides associated with either enzyme function or MHC binding were detected. The postinfection levels of antibody to two GbpB peptides in the N-terminal region of the six GbpB peptides assayed were also elevated (P < 0.031 and P < 0.001). Interestingly, the patterns of the rodent response to GbpB peptides were similar to the patterns seen in salivas from young children during their initial exposure to S. mutans. Thus, the presence of a detectable postinfection salivary IgA response to mutans streptococcal virulence-associated components, coupled with the correspondence between rat and human mucosal immune responsiveness to naturally presented Gtf and GbpB epitopes, suggests that the rat may be a useful model for defining mucosal responses that could be expected in humans. Under controlled infection conditions, such a model could prove to be helpful for unraveling relationships between the host response and oral biofilm development.

Immunological and Microbiologic Changes during Caries Development in Young Children

“…This result could be explained by the fact that GLU is a peptide located in the glucan-binding domain, and that this motif is repeated several times within the C-terminal sequence, which could lead to increased frequency of binding of the IgA antibody with Gtf [Nogueira et al, 2008]. Gtf is essential for S. mutans accumulation as it catalyzes the synthesis of glucan from sucrose.…”

“…Then, the samples were filtered with 0.22-m centrifuge tube filters (Spin-X; CoStar). The reactions of salivary IgA antibody to Gtf, GbpB, peptides derived from these proteins, or SBR were tested using a particle-based multiplex fluorescent immunoassay (Luminex Corp.) [Nogueira et al, 2008]. Fluorescently tagged microspheres with different fluorescent signatures were coated with Gtf, GbpB, one of nine protein-derived peptides, or SBR.…”

An analysis of the role of glucan-binding proteins in Streptococcus mutans biofilm architecture and caries development

“…Rats, like humans, form an immune response to colonization by S. mutans. There have been several studies reporting the immunogenicity of Gbps and Gtfs, as well as the immune response to S. mutans colonization (Smith et al 2003, Zhao et al 2006, Jespersgaard et al 1999, Nogueira et al 2008, Nogueira et al 2005)(Mattos-Graner et al 2006, Zhao et al 2006. Of the glucan-binding proteins examined in this thesis project, only GbpD has been shown to induce an immune response in rodents (Zhao et al 2006).…”

“…However Gtfs and the glucan-binding domain of Gtfs are immunogenic (Nogueira et al 2008) and it is possible that loss of Gbps could expose other antigenic sites on the S. mutans cell wall. It would be of interest to examine the ability of WT and Gbp mutant biofilms to survive challenge from host defenses.…”

Caracterização da resposta imune de mucosas a colonizadores iniciais da cavidade bucal em recém-nascidos a termo e pré-termo: um estudo prospectivo

“…Vários estudos vêm sendo realizados na tentativa de se encontrar proteínas capazes de estimular a produção de anticorpos IgA na saliva contra esses antígenos de superfície e consequentemente reduzir e/ou prevenir a atividade cariogênica (CHILDERS et al, 2002;CHILDERS et al, 1999;HAJISHENGALLIS et al, 1999;CHILDERS et al, 1994;JESPERSGAARD et al, 1999;NOGUEIRA et al, 2008) . Resposta imune a GbpB tem sido encontrada em muitas crianças, mesmo logo após o nascimento (SMITH et al, 1998;SMITH et al, 1997;SMITH et al, 2003), sugerindo o potencial imunogênico desta proteína.…”