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

Fraccarollo, Daniela; Neuser, Jonas; Möller, Julian; Riehle, Christian; Galuppo, Paolo; Bauersachs, Johann

Immature neutrophils and HLA-DRneg/low monocytes expand in cancer, autoimmune diseases and viral infections, but their appearance and functional characteristics after acute myocardial infarction (AMI) remain underexplored. We found an expansion of circulating immature CD16+CD66b+CD10neg neutrophils and CD14+HLA-DRneg/low monocytes in patients with AMI, correlating with cardiac damage, function and serum levels of immune-inflammation markers. Increased frequency of immature CD10neg neutrophils and elevated circulating levels of IFN-γ were linked, mainly in cytomegalovirus (CMV)-seropositive patients with high anti-CMV antibody titers and expanded CD4+CD28null T-cells. At a mechanistic level, CD10neg neutrophils enhance IFN-γ production by CD4+ T-cells through induction of interleukin-12. Moreover, we showed that HLA-DRneg/low monocytes are not immunosuppressive but secrete high levels of pro-inflammatory cytokines after differentiation to macrophages and IFN-γ stimulation. Thus, the immunoregulatory functions of immature CD10neg neutrophils play a dynamic role in mechanisms linking myeloid cell compartment dysregulation, Th1-type immune responses and inflammation in patients with AMI.