Brucella lipopolysaccharide deficiency with lipid A induces robust T cells immune response

Abstract

Brucella, an opportunistic intracellular parasitic bacterium, is classified as a Gram-negative organism. Lipopolysaccharide (LPS), as primary virulence factor of Brucella, includes lipid A, O-antigen, and core polysaccharide, with lipid A being the principal component. The atypical structure of Brucella LPS, noted for its very-long-chain fatty acids, may suppress the host immune response, thus facilitating chronic disease development. The mechanism by which these chains induce immunosuppression remains poorly understood.This study aimed to investigate these chains through deletion of the BacA gene. We extracted LPS to stimulate Bone Marrow-Derived Dendritic Cells (BMDCs) in vitro and co-cultured them with T cells to induce proliferation and differentiation. The in vivo immune response to LPS was evaluated through routine blood tests, CD4 and CD8 assays, and lymphocyte stimulation indices. Our findings demonstrate that wild-type LPS from B. melitensis (Bm-WT) does not elicit an immunostimulatory response in vitro; rather, it promotes immune suppression in vivo. In contrast, LPS derived from B. melitensis with a mutated BacA gene (Bm-ΔBacA) disrupts the immune suppression and encourages the production of inflammatory factors. These findings underscore the crucial role of modifying lipid A through molecular biology techniques to advance bacterial vaccines and adjuvants.