Genome Wide Expression Profiling Reveals Suppression of Host Defence Responses during Colonisation by Neisseria meningitides but not N. lactamica

Abstract

Both Neisseria meningitidis and the closely related bacterium Neisseria lactamica colonise human nasopharyngeal mucosal surface, but only N. meningitidis invades the bloodstream to cause potentially life-threatening meningitis and septicaemia. We have hypothesised that the two neisserial species differentially modulate host respiratory epithelial cell gene expression reflecting their disease potential. Confluent monolayers of 16HBE14 human bronchial epithelial cells were exposed to live and/or dead N. meningitidis (including capsule and pili mutants) and N. lactamica, and their transcriptomes were compared using whole genome microarrays. Changes in expression of selected genes were subsequently validated using Q-RT-PCR and ELISAs. Live N. meningitidis and N. lactamica induced genes involved in host energy production processes suggesting that both bacterial species utilise host resources. N. meningitidis infection was associated with down-regulation of host defence genes. N. lactamica, relative to N. meningitidis, initiates up-regulation of proinflammatory genes. Bacterial secreted proteins alone induced some of the changes observed. The results suggest N. meningitidis and N. lactamica differentially regulate host respiratory epithelial cell gene expression through colonisation and/or protein secretion, and that this may contribute to subsequent clinical outcomes associated with these bacteria.

Lipooligosaccharide Structures of Invasive and Carrier Isolates of Neisseria meningitidis Are Correlated with Pathogenicity and Carriage

“…Overall, it has been increasingly recognized that the suppression of immunity is a component of the response to Gramnegative bacterial septicemia that facilitates infection and leads to a subsequent systemic response and circulatory collapse that is the primary cause of death in industrialized countries. Supporting this concept, genome-wide expression profiling revealed that pathogenic N. meningitidis can suppress host responses (45). Significant evidence indicates that expression of highly phosphorylated, hexaacylated LOS that leads to homeostatic signaling in response to inflammation mediated by NF-B induction by the TIR domain-containing adaptor inducing IFN-␤ (TRIF)/TRIF-related adaptor molecule (TRAM) pathway is critical to the ability of N. meningitidis to induce immune tolerance, evade the host immune system, and cause disease (27,46,47).…”

Recognition of Neisseria meningitidis by the Long Pentraxin PTX3 and Its Role as an Endogenous Adjuvant

“…Meningococcus type B (MenB) is the major cause of invasive meningococcal disease in most countries, with incidence ranging from one case per 100,000 per year to six cases per 100,000 per year, peaking in children between age 6 months and 2 years [ 7 ]. The capacity to colonize human beings efficiently and cause high levels of bacteraemia is dependent on the ability of MenB to evade the immune system [ 8 , 9 ]. MenB has developed several strategies to evade host immune responses, including the expression of a highly dynamic genome and of surface structures which mimic host molecules.…”

Bacterial resistance to antimicrobial peptides an evolving phenomenon

“…But not only enteric pathogens display this strategy. Neisseria gonorrhoeae downregulated the levels of LL-37 in a cervical epithelial cells line ME180, while Neisseria meningitidis downregulated the levels of peptidase inhibitor 3(PI3) in the 16HBE14 bronchial epithelial cell line (134,135).…”