Regulation of cytokine gene expression during Brucella abortus infection

Abstract

Toll-like receptors (TLR) play a key role in antimicrobial host defense. Bacterial cell wall components and lipopolysaccharide (LPS) are recognized by macrophages via TLR, resulting in activation of professional antigen-presenting cells, initiation of acquired immune responses and further elimination of the invasive bacteria. TLR2 and TLR4 have been shown to recognize bacterial components. TLR2 is required for signaling by numerous ligands from gram-negative and gram-positive bacteria such as lipoteichoic acids, peptidoglycan and lipoproteins. In contrast, TLR4 fails to confer responsiveness to gram-positive bacteria and their components, but it is the main LPS signaling receptor. LPS is a major constituent of the outer membrane of gram-negative bacteria, such as Brucella, and is known to activate neutrophils, monocytes, macrophages, and other cell types to up-regulate expression of adhesion molecules and produce a number of pro- and anti-inflammatory cytokines. This study demonstrates that the attenuated strain Brucella abortusRB51 can stimulate cells through TLR4 and MyD88, resulting in NF-kB activation. The virulent strain B. abortus 2308 can also stimulate the cells by a MyD88-dependent pathway without involving either TLR4 or TLR2. It also induced NF-kB activation and nuclear translocation, suggesting that B. abortus RB51 induces activation of the proinflammatory response by a TLR4-dependent pathway with the subsequent NF-kB activation and nuclear translocation; nevertheless, the 2308 strain induced NF-kB nuclear translocation that was activated by an alternative pathway, different from that induced by TLR. Key words: Brucella abortus, RB51, TLR, NF-kB, transduction signals, cytokines.