Interplay between bacteria and host epithelial cells

University dissertation from Stockholm : Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University

Abstract: Bacterial pathogens have developed multiple ways of manipulating host cell functions to exploit the host environment. We found that interactions with epithelial cells increase the resistance of the human pathogen Neisseria meningitidis to the antimicrobial peptide LL-37. This resistance was dependent on host cell cholesterol-rich microdomains and RhoA/Cdc42-dependent signalling.At mucosal surfaces, pathogenic bacteria compete with the resident microbiota. Lactobacillus inhibits the adherence of a wide range of pathogens, however, the mechanisms of inhibition are still largely unknown. We demonstrate that certain lactobacilli interfere with host cell signalling pathways used by pathogenic bacteria during initial colonisation. Inhibitory lactobacilli blocked the pathogen-induced activation of Src, increases of host cytosolic [Ca2+] and upregulation of Egr1, in a TLR2-dependent fashion. We further identify Egr1 as a host factor crucial for efficient pathogen adherence. The pathogens used in these studies were N. meningitidis, Helicobacter pylori and Streptococcus pyogenes.In summary, these studies highlight that the interplay between bacteria and host cells is a critical determinant of pathogenesis and bacterial co-existence in the host.

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