preprint draft Kathrin Tomasek author 3AEC8556-F248-11E8-B48F-1D18A9856A870000-0003-3768-877X Alexander F Leithner author 3B1B77E4-F248-11E8-B48F-1D18A9856A870000-0002-1073-744X Ivana Glatzová author 727b3c7d-4939-11ec-89b3-b9b0750ab74d Michael S. Lukesch author Calin C Guet author 47F8433E-F248-11E8-B48F-1D18A9856A870000-0001-6220-2052 Michael K Sixt author 41E9FBEA-F248-11E8-B48F-1D18A9856A870000-0002-4561-241X CaGu department MiSi department Cellular Navigation Along Spatial Gradients project Mechanical adaptation of lamellipodial actin project 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 dendritic cells as a previously undescribed 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 pathogenic bacteria to CD14 lead to reduced dendritic cell migration and blunted expression of co-stimulatory molecules, both rate-limiting factors of T cell activation. 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. Cold Spring Harbor Laboratory2021 eng 10.1101/2021.10.18.464770 https://research-explorer.ista.ac.at/record/11843 https://research-explorer.ista.ac.at/record/10307 Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>bioRxiv</i>. doi:<a href="https://doi.org/10.1101/2021.10.18.464770">10.1101/2021.10.18.464770</a> K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, BioRxiv (n.d.). K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M. K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory. Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href="https://doi.org/10.1101/2021.10.18.464770">10.1101/2021.10.18.464770</a>. Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &#38; Sixt, M. K. (n.d.). Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href="https://doi.org/10.1101/2021.10.18.464770">https://doi.org/10.1101/2021.10.18.464770</a> Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. bioRxiv, <a href="https://doi.org/10.1101/2021.10.18.464770">10.1101/2021.10.18.464770</a>. Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch, Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href="https://doi.org/10.1101/2021.10.18.464770">https://doi.org/10.1101/2021.10.18.464770</a>. 103162021-11-19T12:24:16Z2026-05-20T22:30:51Z