Immunobiology of Brucella Species Infections

Brucella species are Gram-negative, facultative intracellular bacteria that cause brucellosis, a zoonotic disease of global importance. Upon transmission, Brucella invades professional phagocytes—principally macrophages and dendritic cells—and subverts innate defences by modifying its lipopolysaccharide (LPS) and secreting effector proteins through a dedicated Type IV secretion system (T4SS). These strategies prevent phagolysosomal maturation, attenuate pro-inflammatory signalling and promote bacterial replication within an endoplasmic reticulum–derived niche. Early infection elicits a muted cytokine response, characterised by low levels of tumour necrosis factor-α and interleukin-1β, thereby avoiding rapid clearance. As infection progresses, a Th1-biased adaptive response emerges, with interferon-γ driving macrophage microbicidal activity. However, Brucella-induced interleukin-10 production, T cell exhaustion and expansion of myeloid-derived suppressor cells undermine sustained immunity, facilitating chronic persistence. Antigen presentation is further compromised by impaired maturation of dendritic cells and inhibition of apoptosis in infected cells. Advances in understanding these multilayered evasion mechanisms have informed novel vaccine constructs and host-directed therapies that aim to restore effective cell-mediated responses and resolve persistent infection.

Research from Nature Portfolio

Recent studies have revealed the spatiotemporal organisation of LPS biosynthesis in Brucella abortus, showing that smooth LPS assembly occurs at specific polar and division sites. By mapping the localisation of inner-membrane transport complexes and identifying a bifunctional O-antigen ligase, researchers have uncovered how controlled LPS incorporation underpins outer-membrane integrity and virulence. This refined view of the LPS assembly trajectory highlights potential targets to disrupt Brucella’s stealthy evasion of host pattern-recognition receptors and may inform the development of inhibitors that prevent proper outer-membrane formation, thereby enhancing innate detection and clearance.

Immunobiology of Brucella Species Infections publication trend

The graph below shows the total number of articles in immunobiology of brucella species infections across all publications each year (not limited to Nature Index journals).

Technical terms

Lipopolysaccharide (LPS): a glycolipid forming the outer leaflet of the Gram-negative bacterial envelope that modulates host immune recognition and contributes to virulence.

Type IV secretion system (T4SS): a specialised bacterial apparatus that translocates effector proteins into host cells, altering intracellular trafficking and immune responses.

Myeloid-derived suppressor cells (MDSCs): a heterogeneous population of immature myeloid cells that inhibit T cell activation and promote chronic infection.

Cytokine storm: an excessive and dysregulated release of pro-inflammatory cytokines that can exacerbate tissue damage and immune dysfunction.

Th1 response: a branch of adaptive immunity characterised by interferon-γ production that activates macrophages for intracellular pathogen clearance.

References

1. Establishment of Chronic Infection: Brucella's Stealth Strategy. Frontiers in Cellular and Infection Microbiology (2016).
2. Brucella Modulates Secretory Trafficking via Multiple Type IV Secretion Effector Proteins. PLOS Pathogens (2013).
3. Type IV secretion system of Brucella spp. and its effectors. Frontiers in Cellular and Infection Microbiology (2015).
4. Brucella Control of Dendritic Cell Maturation Is Dependent on the TIR-Containing Protein Btp1. PLOS Pathogens (2008).
5. CD4+ T Cell-derived IL-10 Promotes Brucella abortus Persistence via Modulation of Macrophage Function. PLOS Pathogens (2013).
6. Single‐cell landscape revealed immune characteristics associated with disease phases in brucellosis patients. iMeta (2024).
7. Lipopolysaccharide biosynthesis and traffic in the envelope of the pathogen Brucella abortus. Nature Communications (2023).
8. Copper sensing transcription factor ArsR2 regulates VjbR to sustain virulence in Brucella abortus. Emerging Microbes & Infections (2024).