Human cells rely on various antimicrobial peptides, including defensins, to prevent the spread of pathogenic bacteria. For example, defensins can induce chemotaxis of dendritic cells, and expression of defensins correlates with inhibition of bacterial RNA, DNA and protein synthesis, as well as with reduced bacterial viability. Reporting in the Journal of Experimental Medicine, Brice Sperandio and colleagues now show that Shigella flexneri manages to lower host defences by targeting the expression of host defensins.

The first indication that S. flexneri might affect the expression of antimicrobial peptides was previously reported following the examination of rectal biopsies from patients with bacillary dysentery, which is caused by Shigella spp. Intriguingly, these biopsies had unexpectedly low levels of HBD1 and of another antibacterial peptide, LL37. To confirm these findings, and to elucidate the mechanism by which S. flexneri might affect expression of antimicrobial peptides, Sperandio and colleagues examined the expression of several antimicrobial peptides in two different cell lines upon infection with wild-type S. flexneri and/or with mutant variants. Strikingly, wild-type S. flexneri could modulate the expression of HBD3, LL37 and CCR6. By contrast, mutants that lacked MxiE, a transcriptional activator, could not modulate expression of these genes.

To examine the ability of S. flexneri to modulate antimicrobial peptide expression in greater detail, the authors studied the effects of wild-type and mxiE-mutant S. flexneri variants in an in vivo model of the human intestine. Transcription of 11 host genes — including several defensins, chemokine ligands and chemokine receptors — was decreased upon infection with the wild-type variant compared with the mutant variant. Furthermore, immunostaining experiments revealed that whereas wild-type S. flexneri could diffuse through the mucosal layer in the in vivo model, mxiE-mutants remained trapped at the luminal surface. Moreover, mxiE-mutant-infected cells seemed to recruit dendritic cells, whereas wild-type-infected cells did not.

Taken together, these results suggest that S. flexneri modulates the expression of host antimicrobial peptides through the activity of the MxiE transcription factor. By modulating the expression of these peptides, S. flexneri compromises the ability of infected cells to recruit dendritic cells, thereby enabling thebacteria to effectively colonize the intestine. Evidence suggests that other pathogens, such as Salmonella enterica serovar Typhimurium and Neisseria gonorrhoeae , use similar immune escape strategies, although this has yet to be confirmed. Thus, further work is required to determine whether the strategy that is used by S. flexneri is a general mechanism to evade host defences.