Neutrophil-mediated T-Cell Suppression in Influenza: Novel Finding Raising Additional Questions.
Neutrophil-mediated T-Cell Suppression in Influenza: Novel Finding Raising Additional Questions.
复制标题
流感中中性粒细胞介导的 T 细胞抑制：新发现引发了更多问题。
DOI：
10.1165/rcmb.2017-0425ed
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发表时间：
2018
影响因子：
6.4
通讯作者：
Zemans,RachelL
中科院分区：
文献类型：
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作者：
Zemans,RachelL
Classically, polymorphonuclear neutrophils (PMNs) are viewed as functioning to kill invading microorganisms via phagocytosis, reactive oxygen species, antimicrobial peptides, and neutrophil extracellular traps. However, accumulating evidence indicates that PMNs can also function to modulate the adaptive immune system (1). In fact, as with many cell types, there is increasing recognition of the heterogeneity of neutrophils, with distinct subsets performing specific functions. One subset, consisting of PMN myeloid-derived suppressor cells (PMN-MDSCs), emerges in pathologic conditions and functions to suppress T-cell proliferation and activation. By virtue of T-cell suppression, PMN-MDSCs modulate tumor immunity, autoimmune disease, and infection/sepsis (2–5). PMN-MDSCs are characterized by increased expression of CD11b, arginase 1, and reactive oxygen and nitrogen species, which mediate the suppressor effect (2, 3, 6, 7). Pillay and colleagues previously demonstrated that in humans exposed to endotoxin, a population of CD11bhi PMN-MDSCs emerged and suppressed T-cell proliferation (8). During influenza, T cells become activated, proliferate, and differentiate into effector cells, including cytotoxic CD8 cells, which kill virus-infected cells, resulting in viral clearance but also weight loss and lung injury (9–11). Notably, MDSCs emerge in mice and humans during influenza infection (12). In the context of these findings, Tak and colleagues (pp. 492–499) hypothesized that CD11b+ neutrophils may mitigate lung injury in influenza by suppressing T-cell proliferation. In this issue of the Journal, they demonstrate that Cd11b J/J mice suffer increased weight loss and lung permeability after influenza infection, accompanied by elevated T-cell counts in the lung with no difference in viral clearance (13). This enhanced lung injury appeared to be mediated by T cells, as T-cell depletion rescued the phenotype, restoring weight loss and lung permeability to the levels observed in wild-type mice. Finally, adoptive transfer of Cd11b+/+, but not Cd11b J/J, neutrophils into Cd11b J/J mice also mitigated lung injury with a trend toward diminished T-cell proliferation.This simple yet well-executed study supports the conclusion that CD11b+ neutrophils suppress T-cell proliferation, in turn limiting lung injury, during influenza infection in mice (Figure 1). This finding is an important contribution to the field of myeloidcell suppression of adaptive immunity. However, several questions remain unanswered.
