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Updated: Oct 17, 2026
Legionella pneumophila Outer Membrane Vesicles: Isolation and Analysis of Their Pro-inflammatory Potential on Macrophages
Published on: February 22, 2017
The Neisseria meningitidis lpxL1 mutant induces less tissue factor expression and activity in primary human monocytes
Marit Hellum1,2, Anne-Marie S Trøseid2, Jens P Berg1,2
11 Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Abstract:
Neisseria meningitidis (N. meningitidis) may cause sepsis and meningitis. N. meningitidis with a mutated lpxL1 gene has five, instead of six, acyl chains in the lipid A moiety. Compared with patients infected with the wild type (wt) meningococcus, patients infected with the lpxL1 mutant have a mild meningococcal disease with less systemic inflammation and less coagulopathy. Circulating tissue factor (TF), the main initiator of coagulation, has a central role in the development of coagulation disturbances during sepsis. To study how TF was influenced by the lpxL1 mutant, human primary monocytes and whole blood were incubated with the lpxL1 mutant or the wt meningococcus (H44/76). Monocyte and microvesicle (MV)-associated TF expression and TF-dependent thrombin generation were measured. In both purified monocytes and whole blood, our data show that the lpxL1 mutant is a weaker inducer of monocyte and MV-associated TF compared with the wt. Our data indicate that low levels of circulating TF may contribute to the reduced coagulopathy reported in patients infected with lpxL1 mutants.
Insights
A mutated Neisseria meningitidis (N. meningitidis) with fewer acyl chains causes milder disease. This lpxL1 mutant is a weaker inducer of tissue factor (TF), reducing inflammation and coagulopathy.
Area of Science:
- Microbiology
- Immunology
- Hematology
Background:
- Neisseria meningitidis (N. meningitidis) can cause severe sepsis and meningitis.
- Lipid A's acyl chain number influences N. meningitidis pathogenicity.
- Tissue factor (TF) initiates coagulation and is crucial in sepsis-induced coagulopathy.
Purpose of the Study:
- To investigate the effect of a mutated lpxL1 gene in N. meningitidis on tissue factor (TF) expression and TF-dependent thrombin generation.
- To compare the inflammatory and coagulopathic potential of lpxL1 mutant N. meningitidis with wild-type (wt) strains.
Main Methods:
- Human primary monocytes and whole blood were incubated with either lpxL1 mutant or wt N. meningitidis (H44/76).
- Monocyte and microvesicle (MV)-associated TF expression was measured.
- TF-dependent thrombin generation was assessed.
Main Results:
- The lpxL1 mutant was a weaker inducer of both monocyte and MV-associated TF compared to the wt strain.
- This reduced TF induction was observed in both purified monocytes and whole blood.
- Lower levels of circulating TF were associated with the lpxL1 mutant infection.
Conclusions:
- The lpxL1 mutation in N. meningitidis leads to reduced TF expression and activity.
- This diminished TF response likely contributes to the observed milder meningococcal disease, characterized by less systemic inflammation and coagulopathy.
- Targeting lipid A modification could be a strategy to attenuate meningococcal virulence.
