TH17-derived IL-26 punches holes in bacteria

T_H17 cells have been implicated in host's protection against extracellular bacteria. It is thought that T_H17 cells recruit neutrophils and other granulocytes to the site of bacterial infection who do the job.

However, a new study in Nature Immunology provided evidence that human T_H17 cells can directly eliminate extracellular bacteria via release of IL-26, a cationic peptide that punches holes in bacterial membrane.  

This is actually very well done study. Initially the authors showed that recombinant human IL-26 (rhIL-26) had a direct bactericidal activity in vitro.

Next, the authors showed that rhIL-26 had bactericidal activity in vivo as well.

The authors found that in humans IL-26 expression was restricted to T cells and that out of T cells, T_H17 cells expressed high level of IL-26 and that T_H17 cell supernatant showed IL-26 dependent bactericidal activity.

In addition to its direct bactericidal activity, rhIL-26 could activate human plasmacytoid DCs (pDCs) when combined with dying bacterial DNA.

Interestingly, the authors showed that rhIL-26 could also combine with human DNA and activate pDCs and to a lesser extent monocytes.

Further experiments revealed that rhIL-26 + human DNA conjugate were taken up by pDCs and could signal through TLR9.

Finally, the authors showed that T_H17 cells could activate human pDCs to produce IFN-α via IL-26 + DNA conjugate formation.

In summary, these results provided mechanistic model for direct bactericidal activity of T_H17 cells against extracellular bacteria. In addition, results with IL-26 + hDNA conjugates and pDCs activation revealed how T_H17 cells could be involved in amplification of immune response during autoimmune conditions.    

David Usharauli