IL-12 and related cytokines: function and regulatory implications in Candida albicans infection

Abstract

IL-12 is a cytokine with links to both innate and adaptive immunity systems. In mice, its deletion leads to acute susceptibility to oral infection with the yeast Candida albicans, whereas such mice are resistant to systemic disease. However, it is an essential component of the adaptive response that leads to the generation of Th1-type cytokine responses and protection against disseminated disease. This paper presents an overview of the role of IL-12 in models of systemic and mucosal infection and the possible relationships between them.

Figure 1

A schematic illustrating known and postulated pathways of response to infection with Candida albicans. Interaction with epithelial cells causes the release of cytokines and chemokines that recruit and activate inflammatory and immune cells, including phagocytes, antigen presenting cells (APCs), and T cells. Phagocytic cells engulf the invading fungus and kill via the respiratory burst and cytokine release, whereas APCs process the Candida antigens and migrate to the lymph nodes to present them, in the context of the MHC Class II molecule, to naive CD4 T cells, which are then activated and differentiate to either a Th1-type or a Th17-type cell. The dominant outcome (Th1 or Th17) is probably determined by the prevailing cytokine milieu. On reaching the infected site, Th1 effector cells release cytokines that orchestrate containment of infection to the mucosal surfaces and prevent dissemination. Th17 cells release IL-17, thereby enhancing the candidacidal activity of neutrophils. Thus, both innate and adaptive components of the immune system work cooperatively to provide an effective defence against the invading yeast.