A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host's immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on mouse dendritic cells as a binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of the pathogenic strain CFT073 to CD14 reduced dendritic cell migration by overactivation of integrins and blunted expression of co-stimulatory molecules by overactivating the NFAT pathway, both rate-limiting factors of T cell activation. This response was binary at the single cell level, but averaged in larger populations exposed to both piliated and non-piliated pathogens, presumably via the exchange of immunomodulatory cytokines. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn's disease.
All data are included in the manuscript. Source data are uploaded with this manuscript.
- Michael Sixt
- Michael Sixt
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All animal experiments are in accordance with the Austrian law for animal experiments. Permission was granted by the Austrian Federal Ministry of Science, Research and Economy (identification code: BMWFW 66.018/0010-WF/V/3b/2016). Mice were bred and maintained at the local animal facility in accordance IST Austria Ethical Committee or purchased from Charles River and maintained at the local animal facility in accordance with IST Austria Ethical Committee.
- Ivan Zanoni, Harvard Medical School, United States
© 2022, Tomasek et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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