Fig. 8. Host recognition and response parameters associated with type 1 fimbriae.

Left panel: examples of receptors for type 1 fimbriae. The FimH adhesin binds mannosylated host cell glycoconjugate receptors and activates Toll-like receptor 4 (TLR4) signalling, mainly involving the myeloid differentiation primary response protein 88 (MyD88) adaptor protein arm of this signalling pathway⁶⁰, resulting in pro-inflammatory effects in mice. Binding to uroplakin particles (UP1a, UP1b, UP2 and UP3a) promotes bacterial internalization by mammalian cells; β1 and α3 integrins modulate F-actin dynamics and CD48 receptors trigger TNF responses in mucosal mast cells. Type 1 fimbriae have also been proposed to trigger apoptosis²²³. Middle panel: soluble receptors act as binding antagonists. Soluble IgA immunoglobulins or Tamm–Horsfall protein (THP) (or uromodulin) that carry mannose residues bind FimH and prevent the bacteria from engaging cellular receptors in the urinary tract. Right panel: response of patients to type 1 fimbriated bacteria. The transcriptional response to type 1 fimbriae has been characterized in patients carrying Escherichia coli 83972 fim⁷⁹. E. coli 83972fim acts as a broad inhibitor of RNA processing and translation in human cells. In addition, type 1 fimbriae potentiate ion channel activation and solute carrier expression in the patients. In human cells, FimH triggers increased neurokinin receptor (NK1R) expression. CREB, cAMP response element-binding protein; MGP, mannosylated glycoprotein; NF-κB, nuclear factor-κB; NK, natural killer; P, phosphate group; SP, substance; TF, transcription factor; TIRAP, Toll/interleukin 1 receptor-domain-containing adaptor protein. Adapted from ref.⁶, Springer Nature Limited, and from ref.⁷⁹, CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/).