Cytokines of Innate and Adaptive Immunity to Candida albicans

Abstract

Host defense mechanisms against fungi are numerous and range from relatively primitive and constitutively expressed, nonspecific defenses to sophisticated adaptive mechanisms that are specifically induced during infection (1,2). Although the role of innate immunity was originally considered to be a process for defense of the host early in infection, it is now clear that there is an important reciprocal relationship between innate and adaptive immune responses (2). Cytokines and other mediators play an essential role in this process and, indeed, may not only activate the innate cell population but also drive the adaptive immune response down different pathways of differentiation, ultimately determining the type of effector response that is generated toward pathogens (2–4). Cytokines (including interleukin [IL]-12 and interferon [IFN]-γ) are known to act to stimulate either Thl-type immune responses, which mainly protect against intracellular pathogens, or Th2 responses involved in protection against extracellular pathogens, such as helminths (including IL-4, IL-5, IL-6, IL-10, and IL-13) (5). The cytokine microenvironment also influences innate cell populations, including macrophages, polymorphonuclear neutrophils (PMNs), natural killer (NK) cells, and, particularly, stimulating the differentiation of dendritic cells (DCs) with distinct immunoregulatory properties that may promote Thl- or Th2-type adaptive immune responses (6). To limit the pathologic consequences of an excessive inflammatory cell-mediated immune reaction, the immune system resorts to a number of protective mechanisms, including the reciprocal cross-regulatory effects of Thl- and Th2-type effector cytokines, such as IFN-γ and IL-4 (5). However, Th2-type cytokines may also have strong down regulatory effects on the Thl-promoting properties of innate cells.