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Blood, 1 September 2007, Vol. 110, No. 5, pp. 1406.
Viral infections: beneficial role of eosinophilsBRIGHAM AND WOMEN'S HOSPITAL
In this issue of Blood, Phipps and coworkers present evidence that eosinophils contribute to innate antiviral immunity of the lung without adversely affecting airway hyperresponsiveness.
Because eosinophils are highly dependent on IL-5 for their development,2 IL-5–transgenic (IL-5-Tg) mice contain many more eosinophils in their organs than wild-type mice.3 This situation allows studies to be carried out on IL-5-Tg mice and their wild-type littermates to evaluate the roles of eosinophils in different diseased settings. Due to the fact that IL-5-Tg mice have large numbers of eosinophils in their spleens, the in vivo–differentiated, non-transformed, splenic eosinophils also can be purified from these transgenic animals and then adoptively transferred into wild-type mice to obtain supporting data on the perceived role of the granulocytes. Surprisingly, Phipps and coworkers discovered that IL-5-Tg mice are able to clear RSV significantly better than wild-type mice when the virus is given intranasally. Human eosinophils constitutively express Toll-like receptor 7 (TLR-7),4 which recognizes virus-derived, single-stranded RNA (ssRNA).5 Once the authors discovered that the eosinophils purified from their IL-5-Tg mice also expressed TLR-7, they evaluated what happens to these cells when they encounter ssRNA ex vivo. It was discovered that the ssRNA-treated mouse eosinophils released modest but significant amounts of their granule mediators (eg, eosinophil peroxidase [EPX]). The cells also increased their surface expression of the intregin CD11b/ITGAM. Because MyD88 is an intracellular protein that acts downstream of TLR-7, Phipps and coworkers next created IL-5-Tg mice that lacked MyD88 (MyD88/IL-5-Tg mice). Using an adoptive transfer approach, they showed that MyD88 is needed for the eosinophil's ability to help clear the virus from the mouse's lungs. Interestingly, naive mice that received wild-type eosinophils before RSV infection had diminished airway hyperresponsiveness to methacholine relative to mice that received MyD88-defective eosinophils. Thus, in this situation, functional eosinophils actually dampen airway hyperresponsiveness caused by RSV infection. Finally, the authors report that RSV induces a transient increase in expression of interferon β (IFN-β) and interferon regulatory factor 7 (IRF-7). The latter is a DNA-binding protein that regulates transcription of the former cytokine gene. Based on the accumulated data, the authors conclude that eosinophils actually are beneficial inflammatory cells in the lung during RSV infection as noted in the figure. Although it has been proposed that eosinophils are needed for the efficient elimination of helminth larvae in muscle, this is the first report of a favorable role for granulocytes in a viral infection. Studies were not carried out on human eosinophils. Thus, the biologic relevance of the mouse data to humans remains to be determined. Eosinophils are heterogeneous cells and it is possible that the eosinophils isolated from IL-5-Tg mice behave in a peculiar manner relative to eosinophils isolated from normal mice. Despite these deficiencies, the study by Phipps and colleagues is an important contribution because its findings dramatically change our perception concerning the possible beneficial role of eosinophils in the lung during viral infections.
Footnotes
Conflict-of-interest disclosure: The author declares no competing financial interests.
REFERENCES
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| Copyright © 2007 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
