Interferon gamma directs myelomonocyte accumulation and determines cardiac outcome post myocardial infarction

Myocardial infarction (MI) is characterized by a well-orchestrated sequential inflammatory reaction (1). This immune response is required to clear cellular debris to allow proper wound healing and stable scar formation. Interferons (IFN) are mainly known for their involvement in infectious disease (2), and evidence supporting a role of IFN in cardiovascular disease is accumulating (3, 4). Finger et al. (5) describe for the first time a possible involvement of IFN-γ in the acute phase after MI. They demonstrate that depletion of neutrophils via anti-Gr-1 antibody go along with increased mortality, deteriorated cardiac function, decreased cardiac IFN-γ expression early after MI and reduced presence of inflammatory monocytes (CD11b+/Ly-6G-/Ly-6Chigh), 3 days after MI. IFN-γ-/- mice phenocopied Gr-1+ cell-depleted mice, supporting a regulatory role of IFN-γ on the sequence of inflammatory cell invasion and cardiac outcome early after MI.5 This was further corroborated by the finding that IFN-γ receptor-/- mice exhibited a direct effect on LysM+ cells in cardiac injury post MI. Finally, using IFN-γ reporter mice, the authors could show that IFN-γ expression was expressed in CD4+, CD8+ T cells and NK cells, suggesting that IFN-γ derived from lymphoid cells in the heart directly acts on myelomonocytic cells via IFN-γ receptor 1 and that disruption of this pathway impairs cardiac immune cell accumulation and increases mortality post MI (5).

This paper provides new insights related to the delicate and protective role of IFN-γ in the fine-tuned inflammatory process following MI. At the same time, it asks for further time-dependent evaluation of IFN-γ in different celltypes post MI to get a complete view of the involvement of IFN-γ in the ischemic myocardium. In light of clinical translation, the findings call for studies evaluating whether IFN-γ levels in acute MI patients correlate with their outcome.