Neutrophil–Kupffer-cell interaction in host defenses to systemic infections

doi:10.1016/S0167-5699(98)01319-X

Immunology Today

Volume 19, Issue 11, 1 November 1998, Pages 507-510

Immunology Today

https://doi.org/10.1016/S0167-5699(98)01319-X Get rights and content

Abstract

Most relevant textbooks characterize phagocytosis by Kupffer cells as the principal mechanism for clearing bacterial pathogens from the bloodstream and eliminating them from the liver. Here, Stephen Gregory and Edward Wing discuss recent evidence indicating that the actual mechanism is far more complicated, dependent upon the complex interaction of Kupffer cells with neutrophils that immigrate into the liver following infection.

Section snippets

Kupffer-cell function and blood clearance

Kupffer cells constitute 80–90% of total fixed macrophages in the body[5]. They generally reside within the lumen of the liver sinusoids, adherent to the endothelial lining of the blood vessels, partially obscuring the vascular channel. Kupffer cells are found in greatest number in the periportal area and, therefore, constitute the first macrophage population that comes in contact with bacteria and bacterial products such as endotoxin transported from the gut to the liver[6]. Consequently,

Listeriosis model of systemic infections

Listeria monocytogenes infection in mice is a prototypic model used widely to study host defenses to systemic infections and cellular immunity to intracellular pathogens[12]. The bulk (>60%) of listeriae injected i.v. into mice is cleared rapidly from the bloodstream and can be recovered in the liver 10 min postinoculation2, 13. In nonimmune mice, levels of liver Listeria are reduced by between a third to a tenth of their original value 10 min–6 h postinfection2, 13. The number of bacteria in the

Role of neutrophils in host defenses to systemic bacterial infections

The critical role of neutrophils in host defenses to listerial infections of the liver have gone largely unrecognized until recently. This was, in part, due to the proliferation of bacteria during the early course of infection, despite the presence of a large number of neutrophils within infective foci[2]. Several groups have now demonstrated the importance of neutrophils in host resistance to primary and secondary listerial infections of the liver13, 15, 16, 17. Neutrophil-deficient mice, or

Kupffer cells

Recent experiments indicate that the initial elimination of Listeria taken up in the liver is not solely a function of immigrating neutrophils; Kupffer cells also play a prominent role. Mice depleted of Kupffer cells by pretreatment with liposome-encapsulated dichloromethylene diphosphonate exhibited an approximate 75% decrease in the number of listeriae recovered in the liver 10 min postinfection (S.H. Gregory and E.J. Wing, unpublished). These findings suggest that the majority of Listeria

Conclusion

The accumulated data indicate that the interaction of immigrating neutrophils and Kupffer cells is a critical component of innate host defenses to bacteria cleared by the liver. This relationship is not without precedents. The interaction of neutrophils and Kupffer cells is a major factor contributing to the pathology associated with endotoxemia, septicemia and ischemia followed by reperfusion of the liver seen in the animal models noted above36, 37, 38. The extent of tissue destruction

Acknowledgements

The authors gratefully acknowledge the helpful discussion of T. Carlos (University of Pittsburgh Medical Center) and the financial support of Public Health Service grant RO1DK44367 awarded by the National Institutes of Health.

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ViewpointNeutrophil–Kupffer-cell interaction in host defenses to systemic infections

Abstract

Section snippets

Kupffer-cell function and blood clearance

Listeriosis model of systemic infections

Role of neutrophils in host defenses to systemic bacterial infections

Kupffer cells

Conclusion

Acknowledgements

Gastroenterology

Biochem. Biophys. Res. Commun.

Immunol. Today

J. Exp. Med.

J. Exp. Med.

Infect. Immun.

Infect. Immun.

Infect. Immun.

Infect. Immun.

Infect. Immun.

Infect. Immun.

Annu. Rev. Immunol.

J. Immunol.

J. Leukocyte Biol.

J. Exp. Med.

Infect. Immun.

Infect. Immun.

J. Immunol.

Infect. Immun.

Infect. Immun.

Viewpoint
Neutrophil–Kupffer-cell interaction in host defenses to systemic infections