Abdominal symptoms of invasive meningococcal disease are associated with the induction of plasminogen activator inhibitor-1 in omental adipocytes.

BACKGROUND

Abdominal symptoms are increasingly reported in invasive meningococcal disease (IMD), but the underlying mechanisms remain unclear. We aimed to explore the pathophysiology of these presentations using an animal model.

METHODS

We utilized a collection of 20 meningococcal isolates that were either associated or not associated with abdominal presentations, which were injected intraperitoneally into transgenic mice expressing human transferrin. We employed histological examination, RNA sequencing (RNAseq) transcriptomic analysis, and reverse transcriptase real-time PCR (RT-qPCR) to analyze tissue preparations of the mice's omentum.

RESULTS

The 20 tested isolates promoted similar levels of bacteremia in mice. However, isolates associated with abdominal presentations (mainly serogroup W isolates of clonal complex 11) promoted thrombotic lesions in omental vessels together with higher local expression of IL-6, TNF-α and keratinocyte-derived cytokine (KC). Transcriptomic analysis identified differential regulation of several inflammatory and coagulation-related genes, among which Serpine1 (PAI-1) showed the strongest induction, confirmed by RT-qPCR. In situ RT-PCR localized PAI-1 expression predominantly to omental adipocytes. Purified LOS reproduced many of these inflammatory and transcriptional responses.

CONCLUSIONS

During IMD, thrombosis formation in the omentum's blood vessels is associated with a local induction of an inflammatory response and overexpression of the plasminogen activator inhibitor 1 encoding gene. These observations support a model in which LOS-driven activation of omental adipocytes contributes to a procoagulant microenvironment that may participate in the pathogenesis of abdominal manifestations during IMD.

CLINICAL TRIAL NUMBER: Not applicable.