Changing the paradigm of IFN-γ at the interface between innate and adaptive immunity: Macrophage-derived IFN-γ

IFN-γ plays a critical role in the immune response to bacterial infections. It is established that IFN-γ is mainly produced by NK/ILC1 cells and T cells, and most of papers have rejected the biologic reality of alternative sources for more than 20 years. Here, we are proposing to revisit this dogma and discuss the role of macrophage-derived IFN-γ in bacterial infections. Our hypothesis is based on a panel of publications and is recently revived by our results on placenta, a chimeric organ in which the immune response is tailored to protect the fetus from mother's immune response. The culture of purified placental macrophages is associated with a production of IFN-γ that may contribute to fetal protection from bacterial infections before eliciting a Th1-like immune response potentially pathogenic for pregnancy. Hence, macrophage IFN-γ may be a novel actor of early crosstalk between innate and adaptive immunity in the context of host defense against bacterial infections.