Regulation of Mycobacterium tuberculosis-Dependent HIV-1 Transcription Reveals a New Role for NFAT5 in the Toll-Like Receptor Pathway

Tuberculosis (TB) disease in HIV co-infected patients contributes to increased mortality by activating innate and adaptive immune signaling cascades that stimulate HIV-1 replication, leading to an increase in viral load. Here, we demonstrate that silencing of the expression of the transcription factor nuclear factor of activated T cells 5 (NFAT5) by RNA interference (RNAi) inhibits Mycobacterium tuberculosis (MTb)-stimulated HIV-1 replication in co-infected macrophages. We show that NFAT5 gene and protein expression are strongly induced by MTb, which is a Toll-like receptor (TLR) ligand, and that an intact NFAT5 binding site in the viral promoter of R5-tropic HIV-1 subtype B and subtype C molecular clones is required for efficent induction of HIV-1 replication by MTb. Furthermore, silencing by RNAi of key components of the TLR pathway in human monocytes, including the downstream signaling molecules MyD88, IRAK1, and TRAF6, significantly inhibits MTb-induced NFAT5 gene expression. Thus, the innate immune response to MTb infection induces NFAT5 gene and protein expression, and NFAT5 plays a crucial role in MTb regulation of HIV-1 replication via a direct interaction with the viral promoter. These findings also demonstrate a general role for NFAT5 in TLR- and MTb-mediated control of gene expression

Bazex Syndrome (Acrokeratosis Paraneoplastica) Diagnosed in a Patient with Oral Persistent Ulcerations

Paraneoplastic syndromes associated with head and neck cancer are rare and have been reported under dermatological, endocrine, hematological, neurological and rheumatological disorders. Bazex syndrome is an intriguing paraneoplasia that can be associated with head and neck squamous cell carcinomas. A range of symmetrical dermatological manifestations, with a clear predilection to extremities, that encompasses erythematous squamous plaques, skin scaling and nail dystrophy can provide a psoriasiform pattern in Bazex syndrome. In addition to these tricky clinical features, the rarity of the disease and the lack of understanding on Bazex syndrome generally make such cases to be mismanaged as psoriasis or lichen planus, causing an important delay in the diagnosis of the underlying malignancy. The authors describe a case of Bazex syndrome that occurred in a patient with a recently diagnosed tongue squamous cell carcinoma. Clinicians should consider paraneoplasia when assessing skin and/or oral persistent lesions