Review
Cellular routes of invasion by enteropathogens

https://doi.org/10.1016/S1369-5274(99)00051-XGet rights and content

Abstract

The cellular pathways of infection utilized by pathogenic enteric bacteria have important implications for their clinical manifestations. Yersinia reaches Peyer’s patches via M cells and uses plasmid-encoded factors to resist phagocytic cells. Shigella also translocates via M cells and incapacitates phagocytes, but subsequently re-enters the epithelium basolaterally to elicit an acute inflammatory response. Salmonella has recently been shown to both colonize Peyer’s patches via M cells and independently disseminate to extraintestinal sites via CD18-expressing phagocytes. M cell-mediated entry can lead to gastroenteritis and mucosal antibody production, while systemic dissemination can result in septicemia and elicitation of systemic immune responses.

Introduction

“That inv mutants were able to penetrate into deep tissues without rapid localization into regional lymph nodes indicates that there exists a second invasin-independent pathway responsible for translocation across the intestinal mucosa.” RR Isberg [1]

A single epithelial cell layer separates the host from the lumen of the gastrointestinal tract. In addition to its primary digestive and absorptive functions, the gut-associated epithelium provides an effective barrier that deters commensal, opportunistic and pathogenic microorganisms from establishing infection. The densely packed glycocalyx, mucus coat and apical acidic microenvironment of the intestinal epithelium, together with cell turnover, peristalsis, gastric acidity, lactoferrin, lysozyme, and other antimicrobial peptides, effectively limit microbial access to underlying intestinal mucosa [2]. Furthermore, lymphoid tissue organized in discrete collections under follicle-associated epithelium (FAE) is dispersed throughout the mucosal lamina propria and intercalated between enterocytes to afford specific humoral and cellular protection against mucosal pathogens. Despite this plethora of antimicrobial mechanisms, a number of pathogens have devised strategies to attach, invade and translocate across the gut epithelium. Herein we present a brief overview of the cellular routes of invasion exploited by enteropathogenic Yersinia, Shigella and Salmonella species.

Section snippets

M cell route of invasion

Terminally differentiated M cells specialize in sampling and transporting luminal macromolecules, particulate matter and microbes across FAE to an underlying T lymphocyte-, B lymphocyte-, macrophage- and dendritic cell-rich dome area 3, 4, 5. Reduced brush border and glycocalyx in the apical membranes of M cells facilitate close contact with luminal antigens. In addition, unique patterns of glycosylation of the M cell surface are thought to contribute to their antigenic selectivity and

CD18 route of infection

Several independent lines of evidence point to an M cell-independent pathway of extraintestinal dissemination by enteric pathogens. Despite its inability to invade M cells and enterocytes, damage tight junctions, or reach Peyer’s patches, SPI1-deficient S. typhimurium disseminates extraintestinally and is lethal for mice 39, 40•. Similarly, invasin-deficient Y. enterocolitica does not reach Peyer’s patches and draining mesenteric lymph nodes (MLNs), but remains virulent and capable of

Epithelial route of infection

More than thirty years ago, Takeuchi demonstrated direct epithelial invasion as a route of entry for enteroinvasive bacteria [45]. Access of invasive enteric bacteria to the subepithelial space can be facilitated by polymorphonuclear phagocytes attracted by IL-1, TNFα and pathogen-elicited chemoattractants of epithelial cell origin 46, 47••, 48, 49, 50. Signaling events associated with epithelial invasion and neutrophil infiltration may account for the gastroenteritis associated with certain

Conclusions

Invasive enteric bacteria appear to have at least two basic strategies for translocation across an intact mucosal barrier. Using chromosomally or plasmid-encoded invasins, enteropathogens can enter M cells and enterocytes. In addition, the host can actively translocate enteric pathogens across the epithelium via CD18-expressing phagocytes.

Janus, the Roman god of doorways, is usually portrayed with two faces. In analogous fashion, the M cell and the CD18-positive phagocytes may be viewed as

Acknowledgements

We thank BB Finlay for constructive review of the manuscript prior to publication. Figure 4 was photographed by W Tony Parks. This work was supported by an National Institutes of Health postdoctoral fellowship, grants AI39557 and AI44486, and the James Biundo Foundation.

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

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  • •• of outstanding interest

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