IFN-gamma primes macrophages for enhanced TNF-alpha expression in response to stimulatory and non-stimulatory amounts of microparticulate beta-glucan

Immunol Lett. 2005 Apr 15;98(1):115-22. doi: 10.1016/j.imlet.2004.10.020. Epub 2004 Nov 24.


beta-(1-->3)-D-Glucan is an integral cell wall component of a variety of fungi, plants, and bacteria. Like the prototypic inflammatory mediator lipopolysaccharide (LPS), some beta-(1--> 3)-D-glucan-containing preparations have been shown to induce the production of proinflammatory cytokines by macrophages. In the present study, we have tested a new microparticulate form of beta-(1--> 3)-D-glucan (MG) from Saccharomyces cerevisiae for its ability to induce proinflammatory cytokine secretion in mouse peritoneal macrophages in vitro, and we have examined the effect of IFN-gamma. MG was rapidly phagocytized by peritoneal macrophages, and these MG-treated macrophages upregulated TNF-alpha, IL-6, and IL-1beta mRNAs and secreted these proinflammatory cytokines. IFN-gamma treatment alone did not induce unstimulated macrophages to produce TNF-alpha. However, a 4 h IFN-gamma pretreatment augmented TNF-alpha secretion by peritoneal macrophages subsequently treated with an optimally stimulatory dose of MG. IFN-gamma pretreatment for 2 h followed by thorough washing and a further 2 h incubation without IFN-gamma still resulted in enhanced TNF-alpha production in response to MG, suggesting that IFN-gamma can prime macrophages for a subsequent proinflammatory response. Most interestingly, we found that IFN-gamma pretreatment of peritoneal macrophages enhanced the TNF-alpha response to amounts of MG that were poorly stimulatory or non-stimulatory in the absence of IFN-gamma priming. These data suggest that a synergy between IFN-gamma and beta-glucan may have evolved to lower the threshold of sensitivity of the innate immune response to fungal pathogens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Cytokines / metabolism
  • Female
  • Gene Expression Regulation / physiology
  • Interferon-gamma / metabolism*
  • Lipopolysaccharides / metabolism
  • Macrophages, Peritoneal / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Phagocytosis / physiology
  • Proteoglycans
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*
  • beta-Glucans / metabolism*


  • Cytokines
  • Lipopolysaccharides
  • Proteoglycans
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • beta-Glucans
  • polysaccharide-K
  • Interferon-gamma