Lipopolysaccharide Derived From the Lymphoid-Resident Commensal Bacteria Alcaligenes faecalis Functions as an Effective Nasal Adjuvant to Augment IgA Antibody and Th17 Cell Responses

Yunru Wang, Koji Hosomi, Atsushi Shimoyama, Ken Yoshii, Takahiro Nagatake, Yukari Fujimoto, Hiroshi Kiyono, Koichi Fukase, Jun Kunisawa

doi:10.3389/fimmu.2021.699349

<jats:p><jats:italic>Alcaligenes</jats:italic> spp., including <jats:italic>A. faecalis</jats:italic>, is a gram-negative facultative bacterium uniquely residing inside the Peyer’s patches. We previously showed that <jats:italic>A. faecalis</jats:italic>-derived lipopolysaccharides (<jats:italic>Alcaligenes</jats:italic> LPS) acts as a weak agonist of toll-like receptor 4 to activate dendritic cells and shows adjuvant activity by enhancing IgG and Th17 responses to systemic vaccination. Here, we examined the efficacy of <jats:italic>Alcaligenes</jats:italic> LPS as a nasal vaccine adjuvant. Nasal immunization with ovalbumin (OVA) plus <jats:italic>Alcaligenes</jats:italic> LPS induced follicular T helper cells and germinal center 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 <jats:italic>Alcaligenes</jats:italic> 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 <jats:italic>Alcaligenes</jats:italic> LPS, promoted the production of TNF-α and IL-5 by T cells. Nasal immunization with OVA plus CT, but not <jats:italic>Alcaligenes</jats:italic> LPS, led to increased numbers of neutrophils and eosinophils in the nasal cavity. Together, these findings indicate that the benign nature of <jats:italic>Alcaligenes</jats:italic> LPS is an effective nasal vaccine adjuvant that induces antigen-specific mucosal and systemic immune responses without activation of inflammatory cascade after nasal administration.</jats:p>

Lipopolysaccharide Derived From the Lymphoid-Resident Commensal Bacteria Alcaligenes faecalis Functions as an Effective Nasal Adjuvant to Augment IgA Antibody and Th17 Cell Responses

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