Healthy Carriage or Invasive Disease? -The immunological response to Neisseria meningitidis

Aim: To understand what mechanisms dictating the “healthy carriage” of the potentially fatal pathogen Neisseria meningitidis.

Background: Neisseria meningitidis (meningococcus) is a human specific pathogen that is carried asymptomatically in the pharynx and nasopharynx of approximately 10% of the population. For reasons that are largely unknown, meningococci in susceptible individuals pass into the blood, cross the blood-brain barrier and cause serious conditions such as septicemia and/or meningitis. Adaptive immunity provides good protection against meningococcal disease, but each year about 50-100 people in Sweden are affected by meningococcal infections and in the meningitis belt in sub-Saharan Africa the incidence can be as high as 1% during epidemics. Although an immunocompromised immune system, genetic defects and certain co-infections are known risk factors, the question remains; Why do some people develop severe meningococcal disease while others remain asymptomatic carriers? Despite great efforts to identify virulence factors in Neisseria meningitidis, it is not clearly established what actually causes carriage or invasive disease.

• Since Meningococci colonize the pharynx where epithelial cells constitute the first line of defense against a potential infection,  could it be that these cells and their immunological capacity influence the outcome - invasive disease or harmless carriage?
• Do meningococci belonging to capsular groups with different degrees of virulence produce different immunological activity in the pharyngeal epithelial cells with which they interact?

Outcomes:  This study is the first step towards a hopefully broader understanding of what dictates whether meningococci remain a harmless passenger in our throats or whether they cause fatal disease. Having studied the genome of these bacteria in detail, we now want to turn our focus to the host cells in order to better understand which parameters influence whether the pharynx is colonized to a non-pathological degree and which parameters (or absence thereof) may be involved in failed containment and thus allow invasion. Understanding why some people get sick while others remain healthy is one of the central questions in infectious medicine and for decades, pathogens have been searched for the defining abilities that determine the outcome. By gaining a basic understanding of the crucial host mechanisms, one can move forward to understand inter-individual differences and risk factors.