Pathogenic bacteria adhering to the human vascular wall triggers vascular damage during meningococcal sepsis

January 24, 2013

Researchers at the Paris Cardiovascular Research Center (PARCC) have shown how adhesion of Neisseria (N.) meningitidis to human microvessels in a humanized mouse model leads to the characteristic cutaneous lesions of meningococcal sepsis. This work, published on January 24 in the Open Access journal PLOS Pathogens, is an important demonstration of the direct role of adhesion, specifically Type IV pili mediated adhesion, plays in the development of the disease.

Meningococcal sepsis is a rapidly developing and often fatal infection. Cutaneous lesions, often presenting clinically as purpuric or petechial skin rashes, are a hallmark feature of the infection hence the term purpura fulminans to describe this severe form of sepsis. Understanding the mechanisms behind the development of these lesions is important to understand disease progression because it reveals the underlying mechanisms of the . From the experimental point of view the strict human specificity of N. has long been a limiting factor in the development of relevant in vivo models of this infection and for understanding how the bacteria interact with the blood vessels. It was previously thought that that the large number of circulating bacteria was responsible for the through the release of LPS in particular.

In this research, investigators utilized a humanized mouse model, where human skin, containing an abundance of human microvessels, was grafted onto immunocompromised mice. Grafted mice thus had a hybrid , part mouse, and part human. In this context, N. meningitidis associated exclusively, and in significant numbers, with the human vessels. Once associated with the human vessels the bacteria rapidly led to an endothelial inflammatory response with expression of the human pro- IL-6 and IL-8 and the infiltration of . Vascular events such as clotting, thrombosis, congestion and vascular leak were all observed in the infected human vessels, mimicking the clinical pathology. The combination of these factors led to the development of a purpuric rash in 30% of the infections. The association of the bacteria with the human vessels was shown to be dependent on the adhesive properties of the bacterial Type IV pili, filamentous structures found at the surface of many pathogenic bacteria. Importantly, bacterial mutants deficient for these adhesive structures do not lead to any distinctive pathology despite normal numbers of circulating bacteria.

This work thus leads to a change in the paradigm in our understanding of the disease mechanism, with local adhesion events now considered central to the disease process. Because it recapitulates key features of human infection, the described experimental model opens new avenues of research to further understand the mechanisms of disease and to design new prevention and treatment strategies.

More information: Melican K, Michea Veloso P, Martin T, Bruneval P, Duménil G (2013) Adhesion of Neisseria meningitidis to Dermal Vessels Leads to Local Vascular Damage and Purpura in a Humanized Mouse Model. PLoS Pathog 9(1): e1003139. doi:10.1371/journal.ppat.1003139

Related Stories

Modeling sepsis in newborns

September 6, 2012

Sepsis, or bacterial infection of the bloodstream, is a grave, hard-to-diagnose threat in premature newborns in the NICU. Even when it's detected and treated with antibiotics, its inflammatory effects can harm fragile babies' ...

Recommended for you

Experimental MERS vaccine shows promise in animal studies

July 28, 2015

A two-step regimen of experimental vaccines against Middle East respiratory syndrome (MERS) prompted immune responses in mice and rhesus macaques, report National Institutes of Health scientists who designed the vaccines. ...

Can social isolation fuel epidemics?

July 21, 2015

Conventional wisdom has it that the more people stay within their own social groups and avoid others, the less likely it is small disease outbreaks turn into full-blown epidemics. But the conventional wisdom is wrong, according ...

Lack of knowledge on animal disease leaves humans at risk

July 20, 2015

Researchers from the University of Sydney have painted the most detailed picture to date of major infectious diseases shared between wildlife and livestock, and found a huge gap in knowledge about diseases which could spread ...

IBD genetically similar in Europeans and non-Europeans

July 20, 2015

The first genetic study of inflammatory bowel disease (IBD) to include individuals from diverse populations has shown that the regions of the genome underlying the disease are consistent around the world. This study, conducted ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.