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HERO ID
3240517
Reference Type
Journal Article
Title
NK cells in gamma-interferon-deficient mice suppress lung innate immunity against Mycoplasma spp
Author(s)
Woolard, MD; Hudig, D; Tabor, L; Ivey, JA; Simecka, JW
Year
2005
Is Peer Reviewed?
Yes
Journal
Infection and Immunity
ISSN:
0019-9567
EISSN:
1098-5522
Volume
73
Issue
10
Page Numbers
6742-6751
PMID
16177352
DOI
10.1128/IAI.73.10.6742-6751.2005
Web of Science Id
WOS:000232087600062
Abstract
The purpose of this study was to examine the 100-fold
difference in mycoplasma levels in lungs of gamma interferon knockout (IFN-gamma(-/-)) mice
compared to those seen with wild-type BALB/c mice at 3 days postinfection. NK cells secreted
IFN-gamma; however, their cytotoxic granule extracts failed to kill mycoplasma. We found a
conundrum: the clearance of organisms was as effective in NK-depleted IFN-gamma(-/-) animals as
in wild-type mice (with both IFN-gamma and NK cells). NK+ IFN-gamma(-/-) animals had high
mycoplasma burdens, but, after NK-like cell depletion, mycoplasma numbers Were controlled.
Essentially, IFN-gamma was important in animals with NK-like cells and unimportant in animals
without NK cells, suggesting that IFN-gamma counters deleterious effects of NK-like cells.
Impairment of innate immunity in IFN-gamma(-/-) mice was not due to NK-like cell killing of
macrophages. The increased levels of inflammatory cytokines and neutrophils in lung fluids of NK+
IFN-gamma(-/-) mice were reduced after NK cell depletion. In summary, in the murine model that
resembles chronic human disease, innate immunity to mycoplasma requires IFN-gamma when there are
NK-like cells and the positive effects of IFN-gamma counteract negative effects of NK-like cells.
When imbalanced, NK-like cells promote disease. Thus, it was not the lack of IFN-gamma but the
presence of a previously unrecognized NK-like cell-suppressive activity that contributed to the
higher mycoplasma numbers. It appears that pulmonary NK cells may contribute to the
immunosuppressive environment of the lung, but when needed, these dampening effects can be
counterbalanced by IFN-gamma. Furthermore, there may be instances where perturbation of this
regulatory balance contributes to the susceptibility to and severity of disease.
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