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

Area of Science:

• Immunology
• Cell Biology
• Inflammation Research

Background:

• Acute inflammation typically resolves with macrophage clearance of stimuli and return to homeostasis.
• Traditional resolution models overlook complex immune cell dynamics post-inflammation.

Purpose of the Study:

• To investigate the immune cell landscape following resolution of acute inflammation.
• To understand the role of post-inflammatory immune cells in tissue reprogramming and adaptive immunity.

Main Methods:

• Analysis of leukocyte influx in the peritoneal cavity after low-dose zymosan or bacterial challenge.
• Characterization of distinct mononuclear phagocyte populations (tissue-resident Mφs, monocyte-derived Mφs, moDCs, MDSCs).
• Assessment of T and B lymphocyte populations and their interactions with myeloid cells.

Main Results:

• A second, prolonged wave of leukocyte influx, including diverse myeloid and lymphoid cells, occurs post-resolution.
• Mononuclear phagocytes (resMφs, moMφs) induce regulatory T cell (FoxP3+) development.
• Monocyte-derived dendritic cells (moDCs) drive T-cell proliferation, and resMφs facilitate T-cell contraction.
• Monocyte-derived Mφs persist long-term, influencing subsequent inflammatory responses and tissue reprogramming.

Conclusions:

• Inflammation resolution is not a return to homeostasis but a dynamic transition linking innate and adaptive immunity.
• Persistent myeloid cells and altered lymphocyte populations dictate tissue memory and future inflammatory reactions.
• Resolution involves significant tissue reprogramming beyond simple clearance of inflammatory stimuli.