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Downregulation of bactericidal peptides in enteric infections: A novel immune escape mechanism with bacterial DNA as a potential regulator

Abstract

Antibacterial peptides are active defense components of innate immunity. Several studies confirm their importance at epithelial surfaces as immediate barrier effectors in preventing infection. Here we report that early in Shigella spp. infections, expression of the antibacterial peptides LL-37 and human β-defensin-1 is reduced or turned off. The downregulation is detected in biopsies from patients with bacillary dysenteries and in Shigella- infected cell cultures of epithelial and monocyte origin. This downregulation of immediate defense effectors might promote bacterial adherence and invasion into host epithelium and could be an important virulence parameter. Analyses of bacterial molecules causing the downregulation indicate Shigella plasmid DNA as one mediator.

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Figure 1: Southern-blot analysis of RT-PCR reactions for three gene transcripts.
Figure 2: Immunoperoxidase staining of LL-37 in rectal biopsies during shigellosis using rabbit IgG antisera specific to LL-37 in combination with hematoxylin nuclear counter-staining.
Figure 3: Western-blot analysis with the LL-37 specific antisera on protein extract of biopsies.
Figure 4: RT-PCR and western-blot analyses of LL-37 expression in cell lines.
Figure 5: Expression of LL-37 affected by bacterial DNA.

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Acknowledgements

We thank the participants in the study; N.H. Alam for help with biopsy samples; G. Ara and Sharifunnahar for technical assistance; Masuda and Momtaz for assistance in recruiting patients and control subjects; E. Ólafsson for help with statistical analysis; K. Nilsson for the gift of the U937 cell-line; R.A. Harris for linguistic advice; and B. Axelsson for technical assistance. This study was supported by grants from Swedish Agency for Research Co-operation with Developing Countries (SAREC), Centre for Diarrhoeal Disease Research, Bangladesh, the Swedish Medical Research Council, The Swedish Foundation for Strategic Research, the Swedish Cancer Society, Magnus Bergvall's Foundation, Åke Wiberg's Foundation, Ruth and Richard Julin's Foundation and Prof. Nanna Svartz' Foundation.

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Correspondence to Gudmundur H. Gudmundsson.

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Islam, D., Bandholtz, L., Nilsson, J. et al. Downregulation of bactericidal peptides in enteric infections: A novel immune escape mechanism with bacterial DNA as a potential regulator. Nat Med 7, 180–185 (2001). https://doi.org/10.1038/84627

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