New lessons from old pathogens: what parasitic infections have taught us about the role of nuclear factor-kappaB in the regulation of immunity.

Abstract

The nuclear factor-kappaB (NF-kappaB) family of transcription factors is activated by many infectious and inflammatory stimuli. This family regulates the expression of multiple genes, whose products include cytokines, chemokines, adhesion molecules, and antiapoptotic factors that are important components of the innate and adaptive immune response. A prominent role of NF-kappaB transcription factors in resistance to a variety of infectious diseases was revealed by studies with mice that lack individual family members. However, little is known about the basis for these effects or about the role of individual family members during a coordinated immune response to infection. Diverse parasites such as Toxoplasma gondii, Leishmania major, and Trichuris muris provide a unique opportunity to understand the role of the NF-kappaB system in the development of innate and adaptive immunity to these infections. The basis for resistance and susceptibility to these parasites is well understood, and studies using these experimental systems have provided unique insights into the role of NF-kappaB in the regulation of T-helper 1 cell (Th1) and Th2 type responses. It has become clear that NF-kappaB family members have cell lineage-specific functions and that their relative importance varies with type of infection as well as route of pathogen entry. Thus, studies with models of parasitic infection have revealed that individual NF-kappaB family members perform distinct, nonoverlapping, and biologically significant functions in the regulation of immunity and inflammation.