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大学・研究所にある論文を検索できる 「パイエル板組織内共生菌アルカリゲネス由来LPS/lipid Aのアジュバント応用に関する研究」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。
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パイエル板組織内共生菌アルカリゲネス由来LPS/lipid Aのアジュバント応用に関する研究

Wang, Yun-Ju 大阪大学 DOI:10.18910/88000

2022.03.24

概要

Alcaligenes spp., including A. faecalis, is a gram-negative facultative bacterium uniquely residing inside the Peyer’s patches. We previously showed that A. faecalis-derived lipopolysaccharides (Alcaligenes LPS) acts as a weak agonist of toll-like receptor 4 (TLR4) to activate dendritic cells (DCs) and shows adjuvant activity by enhancing IgG and Th17 responses to systemic vaccination. Here, I examined the efficacy of Alcaligenes LPS as a nasal vaccine adjuvant. Nasal immunization with ovalbumin (OVA) plus Alcaligenes LPS induced follicular T helper cells (Tfh cells) and germinal center (GC) formation in the nasopharynx-associated lymphoid tissue (NALT) and cervical lymph nodes (CLNs), and consequently enhanced OVA-specific IgA and IgG responses in the respiratory tract and serum. In addition, nasal immunization with OVA plus Alcaligenes LPS induced OVA-specific T cells producing IL-17 and/or IL- 10, whereas nasal immunization with OVA plus cholera toxin (CT) induced OVA-specific T cells producing IFN-γ and IL-17, which are recognized as pathogenic type of Th17 cells. In addition, CT, but not Alcaligenes LPS, promoted the production of TNF-α and IL-5 by T cells. Nasal immunization with OVA plus CT, but not Alcaligenes LPS, led to increased numbers of neutrophils and eosinophils in the nasal cavity. Together, these findings indicate the benign nature of Alcaligenes LPS is an effective nasal vaccine adjuvant that induces antigen-specific mucosal and systemic immune responses without activation of inflammatory cascade after nasal administration.

　Lipid A is responsible for biological effect of LPS and has been applied to adjuvant. Here, I also examined adjuvant activity and safety of chemically synthesized Alcaligenes lipid A. Mice subcutaneously immunized with OVA plus Alcaligenes lipid A showed increased levels of OVA-specific serum IgG antibody, comparing to immunization with OVA alone. In addition, Alcaligenes lipid A induced high levels of IL-17 production from splenic CD4+ T cells, suggesting that Alcaligenes lipid A promoted antigen-specific Th17 cell responses as well as Alcaligenes LPS did in nasal immunization. Moreover, Alcaligenes lipid A had little side effects, such as weight loss and fever, reducing number of lymphocytes and platelets. In vitro stimulation with Alcaligenes lipid A upregulated expression of MHCII, CD40, CD80 and CD86 and enhanced the production of cytokine, IL-6, which are involved in inducing antibody production and Th17 cell responses, from murine bone marrow-derived dendritic cells (BMDCs). Also, in human peripheral blood mononuclear cells (PBMCs), stimulation with Alcaligenes lipid A induced the production of cytokines, including IL-6 and IL-1β. These findings suggest that Alcaligenes lipid A is also a safe and applicable synthetic adjuvant for systemic vaccination.

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