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Active Immunization with Extracellular Vesicles Derived from Staphylococcus aureus Effectively Protects against Staphylococcal Lung Infections, Mainly via Th1 Cell-Mediated Immunity.

Choi SJ, Kim MH, Jeon J, Kim OY, Choi Y, Seo J, Hong SW, Lee WH, Jeon SG, Gho YS, Jee YK, Kim YK - PLoS ONE (2015)

Bottom Line: In addition, these EVs have the vaccine adjuvant ability to induce protective immunity such as the up-regulation of co-stimulatory molecules and the expression of T cell polarizing cytokines in antigen-presenting cells.These protective effects were also found in mice that were adoptively transferred with splenic T cells isolated from S. aureus EV-immunized mice, but not in serum transferred mice.Furthermore, this protective effect of S. aureus EVs was significantly reduced by the absence of interferon-gamma, but not by the absence of interleukin-17.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.

ABSTRACT
Staphylococcus aureus is an important pathogenic bacterium that causes various infectious diseases. Extracellular vesicles (EVs) released from S. aureus contain bacterial proteins, nucleic acids, and lipids. These EVs can induce immune responses leading to similar symptoms as during staphylococcal infection condition and have the potential as vaccination agent. Here, we show that active immunization (vaccination) with S. aureus-derived EVs induce adaptive immunity of antibody and T cell responses. In addition, these EVs have the vaccine adjuvant ability to induce protective immunity such as the up-regulation of co-stimulatory molecules and the expression of T cell polarizing cytokines in antigen-presenting cells. Moreover, vaccination with S. aureus EVs conferred protection against lethality induced by airway challenge with lethal dose of S. aureus and also pneumonia induced by the administration of sub-lethal dose of S. aureus. These protective effects were also found in mice that were adoptively transferred with splenic T cells isolated from S. aureus EV-immunized mice, but not in serum transferred mice. Furthermore, this protective effect of S. aureus EVs was significantly reduced by the absence of interferon-gamma, but not by the absence of interleukin-17. Together, the study herein suggests that S. aureus EVs are a novel vaccine candidate against S. aureus infections, mainly via Th1 cellular response.

No MeSH data available.


Related in: MedlinePlus

Role of Toll-like receptor signaling and T cell-derived cytokines on the protective effect of SEV vaccination.For all figures, SEVs (5 μg) and sham (PBS) were injected intramuscularly to mice at weekly intervals for 3 weeks, and then the lethal dose (4.0 × 108 CFU) of S. aureus were challenged oropharyngeally to the immunized mice one week after the last immunization. The survival was monitored every 12 h after the bacterial challenge for 3 days (n = 10 each group). (A) The survival rates of wild type (WT), MyD88-deficient, TLR2-deficient, TLR4-deficient, and TLR9-deficient (all C57BL/6 background) mice after S. aureus challenge. (B) The survival rates of WT, IFN-γ-deficient, and IL-17-deficient (all BABL/c background) mice after S. aureus challenge.
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pone.0136021.g006: Role of Toll-like receptor signaling and T cell-derived cytokines on the protective effect of SEV vaccination.For all figures, SEVs (5 μg) and sham (PBS) were injected intramuscularly to mice at weekly intervals for 3 weeks, and then the lethal dose (4.0 × 108 CFU) of S. aureus were challenged oropharyngeally to the immunized mice one week after the last immunization. The survival was monitored every 12 h after the bacterial challenge for 3 days (n = 10 each group). (A) The survival rates of wild type (WT), MyD88-deficient, TLR2-deficient, TLR4-deficient, and TLR9-deficient (all C57BL/6 background) mice after S. aureus challenge. (B) The survival rates of WT, IFN-γ-deficient, and IL-17-deficient (all BABL/c background) mice after S. aureus challenge.

Mentions: Both the acquired immunity and innate immunity are important in defense against bacterial infection. In innate immunity, antigen recognition is one of the main steps in the antigen-processing of presentation by antigen presenting cells, including DCs. Toll-like receptor (TLR) signaling pathways, with their down-stream signal of Myd88, are the representative signaling pathways and are divided into nine sub-types. To examine the recognition pathway of SEVs in mice, we evaluated survival rate after SEV-immunization in Myd88-/-, TLR2-/-, TLR4-/-, TLR9-/- and wild type (WT) mice after challenge with the lethal dose of S. aureus. Like WT mice, TLR4-/- and TLR9-/- mice immunized with SEVs showed 100% survival rate after the challenge. However, all of the sham-immunized and SEV-immunized Myd88-/- and TLR2-/- mice died within 48 h of the challenge (Fig 6A). These results indicate that the recognition of SEVs in the host innate immunity is dependent on the TLR2 signaling, but not on TLR4 and TLR9.


Active Immunization with Extracellular Vesicles Derived from Staphylococcus aureus Effectively Protects against Staphylococcal Lung Infections, Mainly via Th1 Cell-Mediated Immunity.

Choi SJ, Kim MH, Jeon J, Kim OY, Choi Y, Seo J, Hong SW, Lee WH, Jeon SG, Gho YS, Jee YK, Kim YK - PLoS ONE (2015)

Role of Toll-like receptor signaling and T cell-derived cytokines on the protective effect of SEV vaccination.For all figures, SEVs (5 μg) and sham (PBS) were injected intramuscularly to mice at weekly intervals for 3 weeks, and then the lethal dose (4.0 × 108 CFU) of S. aureus were challenged oropharyngeally to the immunized mice one week after the last immunization. The survival was monitored every 12 h after the bacterial challenge for 3 days (n = 10 each group). (A) The survival rates of wild type (WT), MyD88-deficient, TLR2-deficient, TLR4-deficient, and TLR9-deficient (all C57BL/6 background) mice after S. aureus challenge. (B) The survival rates of WT, IFN-γ-deficient, and IL-17-deficient (all BABL/c background) mice after S. aureus challenge.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4558092&req=5

pone.0136021.g006: Role of Toll-like receptor signaling and T cell-derived cytokines on the protective effect of SEV vaccination.For all figures, SEVs (5 μg) and sham (PBS) were injected intramuscularly to mice at weekly intervals for 3 weeks, and then the lethal dose (4.0 × 108 CFU) of S. aureus were challenged oropharyngeally to the immunized mice one week after the last immunization. The survival was monitored every 12 h after the bacterial challenge for 3 days (n = 10 each group). (A) The survival rates of wild type (WT), MyD88-deficient, TLR2-deficient, TLR4-deficient, and TLR9-deficient (all C57BL/6 background) mice after S. aureus challenge. (B) The survival rates of WT, IFN-γ-deficient, and IL-17-deficient (all BABL/c background) mice after S. aureus challenge.
Mentions: Both the acquired immunity and innate immunity are important in defense against bacterial infection. In innate immunity, antigen recognition is one of the main steps in the antigen-processing of presentation by antigen presenting cells, including DCs. Toll-like receptor (TLR) signaling pathways, with their down-stream signal of Myd88, are the representative signaling pathways and are divided into nine sub-types. To examine the recognition pathway of SEVs in mice, we evaluated survival rate after SEV-immunization in Myd88-/-, TLR2-/-, TLR4-/-, TLR9-/- and wild type (WT) mice after challenge with the lethal dose of S. aureus. Like WT mice, TLR4-/- and TLR9-/- mice immunized with SEVs showed 100% survival rate after the challenge. However, all of the sham-immunized and SEV-immunized Myd88-/- and TLR2-/- mice died within 48 h of the challenge (Fig 6A). These results indicate that the recognition of SEVs in the host innate immunity is dependent on the TLR2 signaling, but not on TLR4 and TLR9.

Bottom Line: In addition, these EVs have the vaccine adjuvant ability to induce protective immunity such as the up-regulation of co-stimulatory molecules and the expression of T cell polarizing cytokines in antigen-presenting cells.These protective effects were also found in mice that were adoptively transferred with splenic T cells isolated from S. aureus EV-immunized mice, but not in serum transferred mice.Furthermore, this protective effect of S. aureus EVs was significantly reduced by the absence of interferon-gamma, but not by the absence of interleukin-17.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.

ABSTRACT
Staphylococcus aureus is an important pathogenic bacterium that causes various infectious diseases. Extracellular vesicles (EVs) released from S. aureus contain bacterial proteins, nucleic acids, and lipids. These EVs can induce immune responses leading to similar symptoms as during staphylococcal infection condition and have the potential as vaccination agent. Here, we show that active immunization (vaccination) with S. aureus-derived EVs induce adaptive immunity of antibody and T cell responses. In addition, these EVs have the vaccine adjuvant ability to induce protective immunity such as the up-regulation of co-stimulatory molecules and the expression of T cell polarizing cytokines in antigen-presenting cells. Moreover, vaccination with S. aureus EVs conferred protection against lethality induced by airway challenge with lethal dose of S. aureus and also pneumonia induced by the administration of sub-lethal dose of S. aureus. These protective effects were also found in mice that were adoptively transferred with splenic T cells isolated from S. aureus EV-immunized mice, but not in serum transferred mice. Furthermore, this protective effect of S. aureus EVs was significantly reduced by the absence of interferon-gamma, but not by the absence of interleukin-17. Together, the study herein suggests that S. aureus EVs are a novel vaccine candidate against S. aureus infections, mainly via Th1 cellular response.

No MeSH data available.


Related in: MedlinePlus