The activation mechanism of Immune cells by Bordetella bronchiseptica-derived substances and their application study

Abstract

Using bacterial-derived lipopolysaccharide (LPS) as an adjuvant (used to boost vaccine immunogenicity) is hampered by side effects, including toxicity and pyrogenicity, necessitating the development of a safer and more effective adjuvant. I have previously confirmed that sonicated Bordetella bronchiseptica (sBb) increases the antigen-presenting capability of dendritic cells (DCs). Moreover, I demonstrated that the Bordetella bronchiseptica-derived LPS (Bb-LPS) is safer than E. coli O26:B6-derived LPS (O26-LPS). In this study, I aimed to understand the structural characteristics of LPS and lipid A extracted from B. bronchiseptica and its effects on DCs. The chemical structural differences and the biological effects of Bb-LPS and O26-LPS on DCs are shown, and the profiles of the two LPS types differ. I also investigated the mechanism of action of sBbs. TNF-α production in DCs and the expression of immune-related surface markers were measured following treatment with TLR2 and 4 signaling inhibitors (ibTLR 2 and 4) TL2-C29 and CLI-095. In DCs treated with sBb and O26-LPS, ibTLR4 significantly reduced TNF- production and MHC class II and CD86 expression. These findings suggest that sBb and O26-LPS mainly induce a TLR4-dependent immune response. Taken together, this study revealed that sBb activates DCs specifically through TLR4 signaling, leading to improved antigen-presenting capability of DCs taken together. This suggests that sBb and Bb-LPS may be used as cost-effective and safe adjuvant candidates to develop vaccines against B. bronchiseptica–related or other diseases.|For decades, 5-fluorouracil, doxorubicin, and vincristine have been used as chemotherapeutic drugs to treat patients with various cancers, such as breast cancer and lymphoma, and their effects on cancer have been well-documented. However, these anticancer drugs cause fatal side effects, including immunosuppression. This study aimed to investigate whether sonicated Bordetella bronchiseptica bacterin (sBb) can attenuate the immunosuppression of spleen cells caused by these chemotherapeutic agents and which subsets of spleen cells were affected. sBb increased the metabolic activity of spleen cells treated with the three anticancer drugs. Cell death analysis using Annexin V/propidium iodide revealed that sBb significantly decreased spleen cell death. Flow cytometry was used to examine spleen cell subsets using a surface marker-specific antibody. In addition, sBb increased nitric oxide production in anticancer drug-related spleen cells (p < 0.0001). Despite the pharmacological effects of anticancer drugs, many patients suffer from the fatal side effects of immunosuppression. These findings add to my understanding of the protective effects of sBb on anticancer drug-treated spleen cells.