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Abstract
Mucosal tissues in the gastrointestinal tract are exposed to a significant number of microorganisms, many of which present a danger to the host. In contrast, the urogenital tract is colonized rather infrequently with bacterial organisms and devoid of physical barriers such as a multilayered mucus or ciliated epithelia, thereby necessitating separate host defense mechanisms. Recurrent urinary tract infection (UTI) represents successful microbial host evasion and poses a major health problem. In recent years, considerable advances have been made in our understanding of the mechanisms underlying the immune homeostasis of the urogenital tract. The system of pathogen-recognition receptors, including the Toll-like receptors, is able to sense danger signaling and thus activate the host immune system of the genitourinary tract. Various soluble antimicrobial molecules, including iron-sequestering proteins, defensins, cathelicidin, and Tamm-Horsfall protein, have been more clearly defined. In addition, involvement of signaling mediators such as cyclic adenosine monophosphate or the circulatory hormone vasopressin in the defense of uropathogenic microbes and maintenance of mucosal integrity has been demonstrated. Beyond this, specific receptors that are hijacked by uropathogenic Escherichia coli in order to enable invasion and survival within the urogenital system, paving the way for chronic forms of UTI, have been identified. The majority of these findings offer novel avenues for conduct of basic and translational research for development of effective therapies against the diverse forms of acute and chronic UTI.
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Fig. 1.
The diversity of molecular mechanisms of urinary epithelial cells. LPS: lipopolysaccharide, TLR: toll-like receptor, GSL: glycosphingolipid, Tcp: toll/ interleukin-1 receptor (TIR)-domain-containing protein, FAK: focal adhesion kinase, CFTR: cystic fibrosis transmembrane conductance regulator.
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