IFN-γ protects from apoptotic neutrophil-mediated tissue injury during acute Listeria monocytogenes infection.
Listeria monocytogenes (LM) is a foodborne Gram-positive intracellular pathogen that can cause listeriosis in humans and animals. Although phagocytes are known to be involved in the response to this infection, the role of neutrophils is not entirely clear. Here, we have demonstrated that soon after LM infection, a large number of IFN-γ-producing neutrophils quickly accumulated in the spleen, blood, and peritoneal cavity. Both in vivo and in vitro experiments demonstrated that neutrophils were an important source of IFN-γ. IFN-γ played a critical protective role against acute LM infection, as demonstrated by the poor survival of Ifng-/- mice. Moreover, IFN-γ promoted bacterial clearance by the neutrophils, thereby inhibiting LM-induced neutrophil apoptosis and spleen damage. In addition to this, IFN-γ could effectively drive macrophage-mediated phagocytosis of apoptotic neutrophils, which was accompanied with TGF-β secretion and was involved in protection against tissue injury. Importantly, by phagocytizing apoptotic neutrophils, macrophages obtained myeloperoxidase, an important bactericidal molecule only produced by neutrophils, which further promoted the antibacterial activity of macrophages. These findings demonstrate that neutrophils are an important source of IFN-γ at the early stage of LM infection, which is characterized by both LM elimination and tissue-protective effects.
['Wang|Guan|G|', 'Lin|Ang|A|', 'Han|Qiuju|Q|', 'Zhao|Huajun|H|', 'Tian|Zhigang|Z|', 'Zhang|Jian|J|0000-0001-5106-1397']
D000818:Animals D017209:Apoptosis D018398:Homeodomain Proteins D007371:Interferon-gamma D008089:Listeria monocytogenes D008088:Listeriosis D008264:Macrophages D051379:Mice D008810:Mice, Inbred C57BL D018345:Mice, Knockout D009504:Neutrophils D009195:Peroxidase D010587:Phagocytosis D016212:Transforming Growth Factor beta
IFN-γ Tissue injury Listeria monocytogenes Neutrophils Macrophages