N. meningitidis and TLR Polymorphisms: A Fascinating Immunomodulatory Network

Abstract

N. meningitidis infections represent a global health problem that can lead to the development of serious permanent sequelae. Although the use of antibiotics and prevention via vaccination have reduced the incidence of meningococcal disease, our understanding regarding N. meningitidis pathogenesis is still limited, especially of those mechanisms responsible for IMD and fulminant or deadly septic shock. These severe clinical presentations occur in a limited number of subjects, whereas about 10% of healthy individuals are estimated to carry the bacteria as a commensal. Since TLR activation is involved in the defense against N. meningitidis, several studies have highlighted the association between host TLR SNPs and a higher susceptibility and severity of N. meningitidis infections. Moreover, TLR SNPs induced variations in immunological responses and in their persistence upon vaccination against meningococcal disease. In the absence of mass vaccination programs, the early identification of risk factors for meningococcal disease would be recommended in order to start immunization strategies and antibiotic treatment in those subjects carrying the risk variants. In addition, it could allow us to identify individuals with a higher risk for severe disease and sequelae in order to develop a personalized healthcare of high-risk subjects based on their genomic profile. In this review, we have illustrated important preliminary correlations between TLR variants and meningococcal susceptibility/severity and with vaccine-induced immune responses.

Human Genetic Variation Influences Enteric Fever Progression

“…Arbour et al found that the individual with both TLR4 Asp299Gly and TLR4 Thr399Ile polymorphisms would be hyporesponsive when challenged with LPS and was less efficient in eliciting distinct innate immune responses [31]. The polymorphic variant of TLR4 also results in an increased susceptibility to other microbial infections, such as Toxoplasma gondii, Cytomegalovirus, Neisseria meningitides, Mycobacterium leprae and other intracellular pathogens [14,49,50]. However, further discussion about this TLR4 polymorphism association with non-Salmonella infectious diseases is not within the scope of this review.…”

species and their complicated relationships with human health

“…However, since the incidence of IMD is much lower than this, other factors are involved in the risk of progressing to IMD after colonisation. This fulcrum rests on the virulence of the isolate and the underlying health of the host 17,18 . Until recently, N. meningitidis was not associated with urogenital disease and was considered to be a transient asymptomatic coloniser of the urogenital compartment.…”