Resolution of acute inflammation bridges the gap between innate and adaptive immunity.

Acute inflammation is traditionally characterised by PMN influx followed by phagocytosing macrophage (Mφs) that clear injurious stimuli leading to resolution and tissue homeostasis. However, using the peritoneal cavity we found that while innate immune-mediated responses to low-dose zymosan or bacteria resolve within days, these stimuli, but not hyper-inflammatory stimuli trigger a previously overlooked second wave of leukocyte influx into tissues that persists for weeks. These cells comprise distinct populations of tissue-resident Mφs (resMφs) Ly6chi monocyte-derived Mφs (moMφs), monocyte-derived dendritic cells (moDCs) and myeloid-derived suppressor cells (MDSCs). Postresolution mononuclear phagocytes were observed alongside lymph node expansion and increased numbers of blood and peritoneal memory T and B lymphocytes. resMφs and moMφs triggered FoxP3 expression within CD4 cells whereas moDCs drive T-cell proliferation. resMφs preferentially clear apoptotic PMNs and migrate to lymph nodes to bring about their contraction in an inducible nitric oxide synthase--dependent manner. Finally, moMφs remain in tissues for months postresolution alongside altered numbers of T cells collectively dictating the magnitude of subsequent acute inflammatory reactions. These data challenge the prevailing idea that resolution leads back to homeostasis and asserts that resolution acts as a bridge between innate and adaptive immunity as well as tissue reprogramming. [ABSTRACT FROM AUTHOR]