IL-32: An Emerging Player in the Immune Response Network against Tuberculosis?

Abstract

Interleukin-32 (IL-32), which was previously called natural killer cell transcript 4, has recently been recognized as a proinflammatory cytokine (see Glossary) [1]. The main sources of IL-32 are natural killer cells, T cells, epithelial cells, and blood monocytes. Four transcripts of IL-32 are known at present. IL-32 has emerged as an important player in innate and adaptive immune responses, and information is emerging on synergism between IL-32 and other well-characterized players in innate immunity. The innate immune response depends on the recognition of pathogen-associated molecular patterns by families of pathogen recognition receptors. The best characterized among these are the Toll-like receptor (TLR) [2] and the nucleotide-binding oligomerization domain (NOD) [3] families of proteins. Recent studies have shown that IL-32 synergizes with NOD1 and NOD2 ligands to stimulate IL-1s and IL-6 release in a caspase-1-dependent manner [4]. These findings are of potential clinical importance in settings where NOD2 plays a protective role, such as in Crohn's disease, where NOD2-dependent production of defensins and cytokines contributes to antimicrobial defense in the gut. These findings are also likely to be of significance in tuberculosis. Individuals homozygous for the 3020ins C NOD2 mutation show a defective cytokine response to Mycobacterium tuberculosis [5]. It is in this context that the study reported by Netea et al. in PLoS Medicine, in which the authors explored the regulation of IL-32 production by primary cells of the immune system, is of potential importance [6].