β-1,3-glucan induces natural killer cell memory-like immunity

Abstract

Natural killer (NK) cells are considered innate lymphocytes that are able to kill pathogenic microorganisms, including bacteria, parasites and fungi as well as virus-infected cells and tumor cells without prior stimulation. Recent studies suggest that they possess a memory-like property to previously encountered pathogens (e.g., cytomegalovirus). We showed that NK cells directly kill Cryptococcus and Candida, which are fatal opportunistic fungi often infecting immunocompromised individuals. We determined that NKp30 is the activating pattern recognition receptor that mediates NK cell killing of these fungi, and that β-1,3-glucan is the ligand for NKp30. Interestingly, we found that soluble β-1,3-glucan enhanced NK cell killing of C. neoformans and C. albicans. Since humans and animals are exposed to β-1,3-glucan through inhalation of components of the cell wall of microbes or consumption of dietary grains, we asked whether isolated β-1,3-glucan plays a role in shaping NK cell immunity. To determine whether β-1,3-glucan induces a training or memory effect, YT cells, an NK cell line, were treated for 24 hours with laminarin or Saccharomyces β-1,3-glucan and cultured for various times. After an initial period of enhanced C. neoformans killing, killing was reduced to the untreated level on the second week after the initial treatment. However, when cryptococcal killing was assessed on the fourth week, a much greater killing was observed compared to the enhanced killing. This suggests that a recall immune response was induced. We conclude that β-1,3-glucan may induce NK cell memory- like immunity.