Protective humoral and CD4+ T cellular immune responses of Staphylococcus aureus vaccine MntC in a murine peritonitis model

Yu, Weiwu; Yao, Di; Yu, Simiao; Wang, Xintong; Li, Xiaoting; Wang, Mengyao; Liu, Shuo; Feng, Zhenyue; Rothenberg, Marc E.; Li, Wanyu; Wang, Lizi; Liu, Wei; Ma, Jingyun; Yu, Liquan; Tong, Chuan; Song, Baifen; Cui, Yudong

doi:10.1038/s41598-018-22044-y

Cited by 28 publications

(31 citation statements)

References 51 publications

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“…In contrast, levels of IFN-g and IL-17A in the serum of immunized mice were increased after bacterial infection, suggesting that immunization with HI was capable of inducing IFN-g-and IL-17A-producing cells and that cellular immunity might also be involved in HI-mediated protection against S. aureus infection. These results are consistent with previous studies reporting that cellular immunity plays essential roles in protective immunity induced by other S. aureus antigens, such as MntC or PBP2a (19,20). Furthermore, MCP-1 is one of the key chemokines that regulates the migration and infiltration of monocytes/macrophages (21), and levels of MCP-1 in each group were similar to those of proinflammatory cytokines, indicating that inflammation in the lungs of HI-immunized mice was decreased compared to that in PBS-immunized mice.…”

Section: Host Immune Response Toward Hi Immunization With Different Adjuvantssupporting

confidence: 93%

Immunodominance of Epitopes and Protective Efficacy of HI Antigen Are Differentially Altered Using Different Adjuvants in a Mouse Model of Staphylococcus aureus Bacteremia

et al. 2021

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HI, a fusion protein that consists of the alpha-toxin (Hla) and the N2 domain of iron surface determinant B (IsdB), is one of the antigens in the previously reported S. aureus vaccine rFSAV and has already entered phase II clinical trials. Previous studies revealed that HI is highly immunogenic in both mice and healthy volunteers, and the humoral immune response plays key roles in HI-mediated protection. In this study, we further investigated the protective efficacy of immunization with HI plus four different adjuvants in a mouse bacteremia model. Results showed that HI-mediated protection was altered in response to different adjuvants. Using antisera from immunized mice, we identified seven B-cell immunodominant epitopes on Hla and IsdB, including 6 novel epitopes (Hla1-18, Hla84-101, Hla186-203, IsdB342-359, IsdB366-383, and IsdB384-401). The immunodominance of B-cell epitopes, total IgG titers and the levels of IFN-γ and IL-17A from mice immunized with HI plus different adjuvants were different from each other, which may explain the difference in protective immunity observed in each immunized group. Thus, our results indicate that adjuvants largely affected the immunodominance of epitopes and the protective efficacy of HI, which may guide further adjuvant screening for vaccine development and optimization.

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Section: Host Immune Response Toward Hi Immunization With Different Adjuvantssupporting

confidence: 93%

Immunodominance of Epitopes and Protective Efficacy of HI Antigen Are Differentially Altered Using Different Adjuvants in a Mouse Model of Staphylococcus aureus Bacteremia

et al. 2021

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“…increased bacterial loads in their main organs after S. aureus infections [46]. The neutralization of IL-17A increases susceptibility to Chlamydia [47,48] and greatly reduces the survival rate of mice infected with Yersinia pestis [49].…”

Section: Discussionmentioning

confidence: 99%

IL-17A Secreted by Th17 Cells Is Essential for the Host against Streptococcus agalactiae Infections

Chen

Yang

et al. 2021

J. Microbiol. Biotechnol.

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Streptococcus agalactiae is an important bacterial pathogen and causative agent of diseases including neonatal sepsis and meningitis, as well as infections in healthy adults and pregnant women. Although antibiotic treatments effectively relieve symptoms, the emergence and transmission of multidrug-resistant strains indicate the need for an effective immunotherapy. Effector T helper (Th) 17 cells are a relatively newly discovered subpopulation of helper CD4 + T lymphocytes, and which, by expressing interleukin (IL)-17A, play crucial roles in host defenses against a variety of pathogens, including bacteria and viruses. However, whether S. agalactiae infection can induce the differentiation of CD4 + T cells into Th17 cells, and whether IL-17A can play an effective role against S. agalactiae infections, are still unclear. In this study, we analyzed the responses of CD4 + T cells and their defensive effects after S. agalactiae infection. The results showed that S. agalactiae infection induces not only the formation of Th1 cells expressing interferon (IFN)-γ, but also the differentiation of mouse splenic CD4 + T cells into Th17 cells, which highly express IL-17A. In addition, the bacterial load of S. agalactiae was significantly increased and decreased in organs as determined by antibody neutralization and IL-17A addition experiments, respectively. The results confirmed that IL-17A is required by the host to defend against S. agalactiae and that it plays an important role in effectively eliminating S. agalactiae . Our findings therefore prompt us to adopt effective methods to regulate the expression of IL-17A as a potent strategy for the prevention and treatment of S. agalactiae infection.

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“…IL-17A is a cytokine that, through the induction of chemokine production, attracts neutrophils to mediate defenses against different pathogens (Akdis et al, 2016)). It has been shown to be involved in S. aureus infection clearance in mice (Chan et al, 2015, Henningsson et al, 2010, Yu et al, 2018, while also seems to be important in human immune responses to S. aureus (Archer et al, 2016, Welch et al, 2015.…”

Section: Introductionmentioning

confidence: 99%

Fracture biomechanics influence local and systemic immune responses in a murine fracture-related infection model

et al. 2021

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Biomechanical stability plays an important role in fracture healing, with unstable fixation being associated with healing disturbances. A lack of stability is also considered a risk factor for fracture-related infection (FRI), although confirmatory studies and an understanding of the underlying mechanisms are lacking. In the present study, we investigate whether biomechanical (in)stability can lead to altered immune responses in mice under sterile or experimentally inoculated conditions. In non-inoculated C57BL/6 mice, instability resulted in an early increase of inflammatory markers such as granulocyte-colony stimulating factor (G-CSF), keratinocyte chemoattractant (KC) and interleukin (IL)-6 within the bone. When inoculated with Staphylococcus epidermidis, instability resulted in a further significant increase in G-CSF, IL-6 and KC in bone tissue. S. aureus infection led to rapid osteolysis and instability in all animals and was not further studied. Gene expression measurements also showed significant upregulation in CCL2 and G-CSF in these mice. IL-17A was found to be up-regulated in all S. epidermidis infected mice, with higher systemic IL-17A cell responses in mice that cleared the infection, which was found to be produced by CD4+ and γδ+ T cells in the bone marrow. IL-17A knock-out (KO) mice displayed a trend of delayed clearance of infection (p=0.22, Fisher Exact Test) and an increase in interferon (IFN)-γ production. Biomechanical instability leads to a more pronounced local inflammatory response, which is exaggerated by bacterial infection. This study provides insights into long-held beliefs that biomechanics are crucial not only for fracture healing, but also for control of infection.

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Protective humoral and CD4+ T cellular immune responses of Staphylococcus aureus vaccine MntC in a murine peritonitis model

Cited by 28 publications

References 51 publications

Immunodominance of Epitopes and Protective Efficacy of HI Antigen Are Differentially Altered Using Different Adjuvants in a Mouse Model of Staphylococcus aureus Bacteremia

Immunodominance of Epitopes and Protective Efficacy of HI Antigen Are Differentially Altered Using Different Adjuvants in a Mouse Model of Staphylococcus aureus Bacteremia

IL-17A Secreted by Th17 Cells Is Essential for the Host against Streptococcus agalactiae Infections

Fracture biomechanics influence local and systemic immune responses in a murine fracture-related infection model

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