The Role of NF-κB Activation During Protection Against Leishmania Infection

Members of the nuclear factor-κB (NF-κB) family of transcription factors regulate a variety of molecules involved in host defense against pathogens. A prominent role of NF-κB in innate and adoptive immunity is based on the regulation of inducible transcription of various genes whose products are essential components of the immune response such as cytokines, chemokines, and adhesion molecules. Since the discovery of the five members of the NF-κB transcription factor family, RelA, c-Rel, RelB, p50 and p52, considerable progress has been made toward better understanding how the different NF-κB homo- and heterodimers regulate such distinct subsets of target genes. All of the NF-κB molecules are activated by various infectious stimuli; however, there are still open questions related to the selective functions of individual NF-κB family members during a coordinated immune response to infection. Diverse parasites such as Toxoplasma gondii, Leishmania donovani, Leishmania major, and Trichuris muris have been reported to activate NF-κB signaling cascades, and a number of distinct parasite-derived molecules may actively interfere with the pathways that lead to NF-κB activation. In this review, we provide an overview on the role of NF-κB activation in leishmaniasis and discuss how individual NF-κB family members might perform their distinct and non-overlapping functions in the regulation of protective immunity to Leishmania infection.