Related Experiment Videos
Bordetella pertussis infection of human monocytes inhibits antigen-dependent CD4 T cell proliferation
J S Boschwitz1, J W Batanghari, H Kedem
1Department of Microbiology and Immunology, Stanford University School of Medicine, California, USA.
Abstract:
Human monocytes and macrophages bind Bordetella pertussis through multiple specific receptor-ligand interactions; however, the effect of these interactions on monocyte and macrophage function is not well understood. In an in vitro system, B. pertussis infection of human monocytes significantly impaired T cell proliferation to exogenous antigen at MOIs as low as 1.0. B. pertussis isogenic mutant strains deficient in filamentous hemagglutinin or adenylate cyclase toxin were incapable of proliferation inhibition, suggesting that these virulence-associated factors are essential for this activity. B. pertussis-induced monocyte death alone did not explain these results, nor did differences in intracellular survival. In addition, B. pertussis infection did not significantly alter monocyte phagocytosis of complement-opsonized latex particles, indicating that B. pertussis infection does not globally impair monocyte functions in this system. These results suggest that B. pertussis may be capable of subverting cellular immune defenses in an infected host.
Insights
Bordetella pertussis infection impairs T cell proliferation by targeting human monocytes. Key virulence factors, filamentous hemagglutinin and adenylate cyclase toxin, are essential for this immune evasion mechanism.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Human monocytes and macrophages interact with Bordetella pertussis via specific receptor-ligand binding.
- The impact of these interactions on monocyte and macrophage functions remains incompletely understood.
Purpose of the Study:
- To investigate the effect of Bordetella pertussis infection on human monocyte function, specifically T cell proliferation.
- To identify the Bordetella pertussis virulence factors responsible for modulating monocyte-mediated immune responses.
Main Methods:
- In vitro infection of human monocytes with Bordetella pertussis at various multiplicities of infection (MOIs).
- Assessment of T cell proliferation in response to exogenous antigen following B. pertussis infection.
- Utilized isogenic mutant strains deficient in filamentous hemagglutinin or adenylate cyclase toxin.
- Evaluated monocyte death and intracellular bacterial survival.
- Assessed monocyte phagocytosis of complement-opsonized latex particles.
Main Results:
- Bordetella pertussis infection significantly inhibited T cell proliferation at MOIs as low as 1.0.
- Mutant strains lacking filamentous hemagglutinin or adenylate cyclase toxin did not inhibit proliferation, indicating these factors are crucial.
- Monocyte death and intracellular survival differences did not account for the observed inhibition.
- Monocyte phagocytosis of opsonized particles remained largely unaffected, suggesting specific, not global, functional impairment.
Conclusions:
- Bordetella pertussis employs specific virulence factors, filamentous hemagglutinin and adenylate cyclase toxin, to subvert T cell proliferation mediated by human monocytes.
- These findings suggest a mechanism by which Bordetella pertussis evades host cellular immune defenses during infection.