Alternatively activated macrophages elicited by helminth infection can be reprogrammed to enable microbial killing

Mylonas, K. J., Nair, M. G., Prieto-Lafuente, L., Paape, D. and Allen, J. E. (2009) Alternatively activated macrophages elicited by helminth infection can be reprogrammed to enable microbial killing. Journal of Immunology, 182(5), pp. 3084-3094. (doi: 10.4049/jimmunol.0803463) (PMID:19234205)

Abstract

The prime function of classically activated macrophages (activated by Th1-type signals, such as IFN-γ) is microbial destruction. Alternatively activated macrophages (activated by Th2 cytokines, such as IL-4 and IL-13) play important roles in allergy and responses to helminth infection. We utilize a murine model of filarial infection, in which adult nematodes are surgically implanted into the peritoneal cavity of mice, as an in vivo source of alternatively activated macrophages. At 3 wk postinfection, the peritoneal exudate cell population is dominated by macrophages, termed nematode-elicited macrophages (NeMφ), that display IL-4-dependent features such as the expression of arginase 1, RELM-α (resistin-like molecule α), and Ym1. Since increasing evidence suggests that macrophages show functional adaptivity, the response of NeMφ to proinflammatory Th1-activating signals was investigated to determine whether a switch between alternative and classical activation could occur in macrophages differentiated in an in vivo infection setting. Despite the long-term exposure to Th2 cytokines and antiinflammatory signals in vivo, we found that NeMφ were not terminally differentiated but could develop a more classically activated phenotype in response to LPS and IFN-γ. This was reflected by a switch in the enzymatic pathway for arginine metabolism from arginase to inducible NO synthase and the reduced expression of RELM-α and Ym1. Furthermore, this enabled NeMφ to become antimicrobial, as LPS/IFN-γ-treated NeMφ produced NO that mediated killing of Leishmania mexicana. However, the adaptation to antimicrobial function did not extend to key regulatory pathways, such as IL-12 production, which remained unaltered.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Paape, Dr Daniel
• Authors: Mylonas, K. J., Nair, M. G., Prieto-Lafuente, L., Paape, D., and Allen, J. E.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Journal of Immunology
• Publisher: Elsevier
• ISSN: 0022-1767
• ISSN (Online): 1872-7905