Expansion of CD10neg neutrophils and CD14+HLA-DRneg/low monocytes driving proinflammatory responses in patients with acute myocardial infarction

被引:23
作者
Fraccarollo, Daniela [1 ]
Neuser, Jonas [1 ]
Moeller, Julian [1 ]
Riehle, Christian [1 ]
Galuppo, Paolo [1 ]
Bauersachs, Johann [1 ]
机构
[1] Hannover Med Sch, Dept Cardiol & Angiol, Hannover, Germany
来源
ELIFE | 2021年 / 10卷
关键词
CD4(+)CD28(NULL) T-CELLS; SUBSETS; MICE; CYTOMEGALOVIRUS; POLARIZATION; MACROPHAGES; PHENOTYPE; INFECTION; REVEALS;
D O I
10.7554/eLife.66808
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Immature neutrophils and HLA-DRneg/low monocytes expand in cancer, autoimmune diseases and viral infections, but their appearance and immunoregulatory effects on T-cells after acute myocardial infarction (AMI) remain underexplored. We found an expansion of circulating immature CD16(+)CD66b(+)CD(10neg) neutrophils and CD14(+)HLA-DRneg/low monocytes in AMI patients, correlating with cardiac damage, function and levels of immune-inflammation markers. Immature CD10(neg) neutrophils expressed high amounts of MMP-9 and S100A9, and displayed resistance to apoptosis. Moreover, we found that increased frequency of CD10neg neutrophils and elevated circulating IFN-gamma levels were linked, mainly in patients with expanded CD4(+)CD28(null) T-cells. Notably, the expansion of circulating CD4(+)CD28(null) T-cells was associated with cytomegalovirus (CMV) seropositivity. Using bioinformatic tools, we identified a tight relationship among the peripheral expansion of immature CD10(neg) neutrophils, CMV IgG titers, and circulating levels of IFN-gamma and IL-12 in patients with AMI. At a mechanistic level, CD10(neg) neutrophils enhanced IFN-gamma production by CD4(+)T-cells through a contact-independent mechanism involving IL-12. In vitro experiments also highlighted that HLA-DRneg/low monocytes do not suppress T-cell proliferation but secrete high levels of pro-inflammatory cytokines after differentiation to macrophages and IFN-gamma stimulation. Lastly, using a mouse model of AMI, we showed that immature neutrophils (CD11b(pos) Ly6G(pos) CD101(neg) cells) are recruited to the injured myocardium and migrate to mediastinal lymph nodes shortly after reperfusion. In conclusion, immunoregulatory functions of CD10(neg) neutrophils play a dynamic role in mechanisms linking myeloid cell compartment dysregulation, Th1-type immune responses and inflammation after AMI.
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页数:31
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