The TLR7/IRF-5 axis sensitizes memory CD4+ T cells to Fas-mediated apoptosis during HIV-1 infection.

HIV-1 infection is characterized by inflammation and a progressive decline in CD4+ T cell count. Despite treatment with antiretroviral therapy (ART), the majority of people living with HIV (PLWH) maintain residual levels of inflammation, a low degree of immune activation, and higher sensitivity to cell death in their memory CD4+ T cell compartment. To date, the mechanisms responsible for this high sensitivity remain elusive.

Potential T Cell-Intrinsic Regulatory Roles for IRF5 via Cytokine Modulation in T Helper Subset Differentiation and Function.

Interferon Regulatory Factor 5 (IRF5) is one of nine members of the IRF family of transcription factors. Although initially discovered as a key regulator of the type I interferon and pro-inflammatory cytokine arm of the innate immune response, IRF5 has now been found to also mediate pathways involved in cell growth and differentiation, apoptosis, metabolic homeostasis and tumor suppression. Hyperactivation of IRF5 has been implicated in numerous autoimmune diseases, chief among them systemic lupus erythematosus (SLE).

The Siderophore Synthetase IucA of the Aerobactin Biosynthetic Pathway Uses an Ordered Mechanism.

Biosynthesis of the hydroxamate siderophore aerobactin requires the activity of four proteins encoded within the operon. Recently, we biochemically reconstituted the biosynthetic pathway and structurally characterized IucA and IucC, two enzymes that sequentially couple N-acetyl-N-hydroxylysine to the primary carboxylates of citrate. IucA and IucC are members of a family of non-ribosomal peptide synthetase-independent siderophore (NIS) synthetases that are involved in the production of other siderophores, including desferrioxamine, achromobactin, and petrobactin.

Structural and functional delineation of aerobactin biosynthesis in hypervirulent .

Aerobactin, a citryl-hydroxamate siderophore, is produced by a number of pathogenic Gram-negative bacteria to aid in iron assimilation. Interest in this well-known siderophore was reignited by recent investigations suggesting that it plays a key role in mediating the enhanced virulence of a hypervirulent pathotype of (hvKP). In contrast to classical opportunistic strains of , hvKP causes serious life-threatening infections in previously healthy individuals in the community.