Contribution of a Streptococcus mutans Antigen Expressed by a Salmonella Vector Vaccine in Dendritic Cell Activation

Abstract

A Salmonella vector vaccine expressing the saliva-binding region (SBR) of the adhesin AgI/II of Streptococcus mutans has been shown to induce a mixed Th1/Th2 anti-SBR immune response in mice and to require Toll-like receptor 2 (TLR2), TLR4, and MyD88 signaling for the induction of mucosal anti-SBR antibody responses. Since dendritic cells (DC) are critical in innate and adaptive immunity, the present study assessed the role of SBR expression by the vector vaccine in DC activation. Bone marrow-derived DC from wild-type and TLR2, TLR4, and MyD88 knockout mice were stimulated with Salmonella vector BRD509, the SBR-expressing Salmonella vector vaccine BRD509(pSBRT7), or SBR protein, and the DC responses to different stimuli were compared by assessing costimulatory molecule expression, cytokine production, and signaling pathways. The DC response to both BRD509(pSBRT7) and BRD509 was dependent mainly on TLR4. BRD509(pSBRT7) and BRD509 induced upregulation of CD80, CD86, CD40, and major histocompatibility complex class II (MHC II) expression. Lower levels of interleukin-10 (IL-10) and IL-12p40 were produced by BRD509(pSBRT7)-stimulated DC than by BRD509-stimulated DC. Furthermore, BRD509(pSBRT7)-stimulated DC showed decreased p38 phosphorylation compared to that induced by DC stimulated with BRD509. However, BRD509(pSBRT7)-treated DC produced a higher level of IL-6 than BRD509-stimulated cells. The low IL-12p40 and high IL-6 cytokine profile expressed by BRD509(pSBRT7)-stimulated DC may represent a shift toward a Th2 response, as suggested by the increased expression in Jagged-1. These results provide novel evidence that a heterologous protein expressed by a Salmonella vector vaccine can differentially affect DC activation.

Dormant bacteria within Staphylococcus epidermidis biofilms have low inflammatory properties and maintain tolerance to vancomycin and penicillin after entering planktonic growth

“…Although no change in effect was observed for the BMDC surface phenotype induced by the differently grown S. epidermidis cells, bacteria obtained from biofilms with higher proportions of dormant cells induced lower production of TNF-α, IL-12 and IL-6 (). A disparate effect on cytokine production by murine dendritic cells upon stimulation with bacterial preparations that induced expression of CD80 and CD86 to indistinguishable levels was also found elsewhere (Xu et al , 2011). It is noteworthy that bacteria obtained from low dormancy biofilms induced cytokine production by BMDCs to the same extent as bacteria obtained from planktonic cultures.…”

Subversion and Utilization of Host Innate Defense by Leishmania amazonensis

“…They found that the iscl- null mutants of L. major completely abolished their virulence in BALB/c mice, partially due to parasite’s defects in survival under an acid pH condition; however, a low number of mutant parasites could persist in the injection site for several months (Zhang et al, 2009; Xu et al, 2011). In sharp contrast, the iscl- deficient L. amazonensis are fully virulent in BALB/c mice, but are partially attenuated in C57BL/6 mice (K. Zhang, personal communication).…”

Identification of a Supramolecular Functional Architecture of Streptococcus mutans Adhesin P1 on the Bacterial Cell Surface

“…AgI/II family molecules are considered to mediate bacterial adhesion to mucosal glycoproteins (9 -13) as well as to the extracellular matrix (14 -17) and other bacteria (18 -21). The contribution of P1 to bacterial adherence, colonization, and cariogenicity and its promise in clinical trials make it a therapeutic target and focus of immunization studies (22)(23)(24)(25)(26). In the oral environment within the salivary pellicle on tooth surfaces, S. mutans P1 interacts primarily with the glycoprotein salivary agglutinin complex (SAG) comprising predominantly the scavenger receptor gp340/DMBT1 (11-13, 22, 27-37).…”