Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity

The Journal of Clinical Investigation 115, 66-75, 2005

Speaker：李昭鋐                        Time：13：10~14：00, May 4, 2004

Commentator：黎煥耀 老師                               Place：Room 601

Abstract：

There are a huge amount of bacteria in our intestine. But why the commensal bacteria of gut are not eradicated by immune cells or cause inflammation. There are some mechanisms involved in it. Other studies focus on bacteria but not on immune issue.  Previous finding suggests that the intestinal macrophages lack the receptors (CD14) for lipopolysaccharide and Fcα receptor (CD89) for IgA-mediated activities¹. Thus, the authors extend the finding to show that many innate response and growth factor receptors are downregulated on resident intestinal macrophages, and the production of all major proinflammatory cytokines are also downregulated. But this macrophages still retain phagocytic and bacteriocidal activity for Salmonella typhimurium and Escherichia coli. This raises a question why intestinal macrophages derived from blood monocytes are so distinct from blood monocytes. The authors show that factors released by laminar propria stromal cells downregulate monocyte expression of proinflammatory receptors. The cells also reduce the production of proinflammatory cytokines through the activity of TGF-β. This changes blood monocytes to have the phenotype and functional profile of intestinal macrophages. These findings explain that proinflammatory blood monocytes recruited to the intestinal mucosa retain host defense functions but “inflammatory anergy,” so inflammation can not be elicited when they are close to a lot of immunostimulatory bacteria.  

References：

1. Smith, P.D., et al. 2001. Intestinal macrophages lack CD14 and CD89 and consequently are downregulated for LPS- and IgA-mediated activities. J. Immunol.

167:2651–2656.

2. T. MacDonald, et al. 2005. Immunity, inflammation, and allergy in the gut. Science. 307:1920-1925.

3. Lesley E. Smythies, et al. 2005. Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity. J. Clin. Invest.

115:66-75.