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

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

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.699349

DOI=10.3389/fimmu.2021.699349

ISSN=1664-3224

ABSTRACT=<p><italic>Alcaligenes</italic> spp., including <italic>A. faecalis</italic>, is a gram-negative facultative bacterium uniquely residing inside the Peyer’s patches. We previously showed that <italic>A. faecalis</italic>-derived lipopolysaccharides (<italic>Alcaligenes</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 <italic>Alcaligenes</italic> LPS as a nasal vaccine adjuvant. Nasal immunization with ovalbumin (OVA) plus <italic>Alcaligenes</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 <italic>Alcaligenes</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 <italic>Alcaligenes</italic> LPS, promoted the production of TNF-α and IL-5 by T cells. Nasal immunization with OVA plus CT, but not <italic>Alcaligenes</italic> LPS, led to increased numbers of neutrophils and eosinophils in the nasal cavity. Together, these findings indicate that the benign nature of <italic>Alcaligenes</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.</p>