The obligate human pathogen Neisseria meningitidis asymptomatically colonizes the upper respiratory tract, but crossing of the epithelial barrier can cause life-threatening meningitis and/or sepsis. N. meningitidis encounters numerous environmental challenges during colonization in the host, and has evolved different evasion strategies and virulence factors to ensure its survival. In contrast, Lactobacillus species are part of the human microbiota and their commensal colonization confers many benefits to the host, including the inhibition of pathogens.

The first cell type encountered by invading bacteria are epithelial cells and immune cells, which can effectively sense and respond to the presence of bacteria by alerting the immune system or by release of antimicrobial peptides. Antimicrobial peptides are small peptides that are able to directly kill bacteria, but also play a role in modulation of immune responses.  

This thesis focuses on the interaction between the human host and bacteria. Paper I shows that epithelial colonization by different bacterial species induces the transcription factor early growth response protein 1 (EGR1). Induction of EGR1 is mediated primarily by signaling through EGFR and ERK1/2 pathway. In paper II the ability of N. meningitidis and Lactobacillus to modulate expression of antimicrobial peptide human beta-defensin 2 (hBD2) in epithelial cells is compared. Expression of hBD2 is upregulated by lactobacilli. In contrast, N. meningitidis dampens this effect, likely mediated by induction of the host molecule A20, a negative regulator of NF-κB. Since N. meningitidis is susceptible to hBD2-mediated killing, exploitation of A20 may be an immune evasion mechanism. In paper III we demonstrate that hBD2 is able to kill N. meningitidis without causing membrane permeabilization. N. meningitidis DNA can bind hBD2 and thereby inhibit hBD2-mediated killing, presenting a possible evasion mechanism. Finally, paper IV shows that the absence of D-lactate dehydrogenase LdhA in N. meningitidis promotes aggregation and biofilm formation through increased autolysis-mediated release of extracellular DNA.