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Review
. 2008 Nov;10(11):2151-8.
doi: 10.1111/j.1462-5822.2008.01192.x. Epub 2008 Jun 23.

Intracellular microbes and haemophagocytosis

Eugenia Silva-Herzog  1 , Corrella S Detweiler
Affiliations
Review

Intracellular microbes and haemophagocytosis

Eugenia Silva-Herzog et al. Cell Microbiol. 2008 Nov.

Abstract

Haemophagocytosis (hemophagocytosis) is the phenomenon of activated macrophage consumption of red and white blood cells, including professional phagocytes and lymphocytes. It can occur in patients with severe cases of intracellular microbial infection, including avian influenza, leishmaniasis, tuberculosis and typhoid fever. While well-known to physicians since at least the mid-1800s, haemophagocytosis has been little studied due to a paucity of tractable animal and cell culture models. Recently, haemophagocytosis has been described in a mouse model of typhoid fever, and it was noted that the infectious agent, Salmonella enterica, resides within haemophagocytic macrophages in mice. In addition, a cell culture model for haemophagocytosis revealed that S. enterica preferentially replicate in haemophagocytic macrophages. This review describes how, at the molecular and cellular levels, S. enterica may promote and take advantage of haemophagocytosis to establish long-term systemic infections in mammals. The role, relevance and possible molecular mechanisms of haemophagocytosis are discussed within the context of other microbial infections and of genetic deficiencies in which haemophagocytosis occurs and is associated with morbidity.

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Figures

Fig. 1
Fig. 1
Model for the development of haemophagocytosis in S. enterica-infected mice. A.S. enterica (green) resides within macrophage vacuoles. B. The bacteria kill the macrophage via pyroptosis, releasing the inflammatory cytokines IL-18 and IL-1β. Early in infection, IL-18 and IL-1β stimulate NK and NKT cells to produce IFNγ. After the onset of adaptive immunity, T-cells (CD4 and CD8) also produce IFNγ. C. Positive feedback loops, including IL-12 stimulation of NK, NKT and T-cells, help maintain IFNγ production. D. IFNγ stimulates macrophages to phagocytose non-adherent cells. E. Haemophagocytic macrophages may provide S. enterica with a survival niche. It is unknown whether S. enterica reside within vacuoles in haemophagocytic macrophages, as drawn.
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