PMC:3320587 / 1528-2486 JSONTXT

{"project":"sentences","denotations":[{"id":"T11","span":{"begin":0,"end":134},"obj":"Sentence"},{"id":"T12","span":{"begin":135,"end":316},"obj":"Sentence"},{"id":"T13","span":{"begin":317,"end":489},"obj":"Sentence"},{"id":"T14","span":{"begin":490,"end":710},"obj":"Sentence"},{"id":"T15","span":{"begin":711,"end":958},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"The major cause of AIDS deaths globally has been tuberculosis (TB), which is caused by the bacterium Mycobacterium tuberculosis (MTb). Co-infection with MTb exacerbates human immunodeficiency virus type1 (HIV-1) replication and disease progression via both innate and adaptive host immune responses to MTb infection. In this report, we present evidence that the transcription factor NFAT5 plays a crucial role in MTb-induced HIV-1 replication in human peripheral blood cells and monocytes. We also show that MTb infection itself stimulates NFAT5 gene expression in human monocytes and that its expression involves the TLR signalling pathway and requires the downstream adaptor proteins MyD88, IRAK1, and TRAF6. This identification of a novel role for NFAT5 in TB/HIV-1 co-infection reveals that NFAT5 is a major mediator of TLR-dependent gene expression and thus provides a potential new therapeutic target for treatment of HIV-1 and possibly other diseases."}