Identification and characterization of novel infection associated transcripts in macrophages

ABSTRACT Regulated expression of genes in response to internal and external stimuli is primarily responsible for the enormous plasticity and robustness of biological systems. Recent studies have elucidated complex regulatory non protein coding transcript (lncRNA) circuits in coordinated response of immune cells. By analysis of lncRNA expression profiles of macrophages in response to Mtb infection, we identified novel highly expressed transcripts, unique in encompassing one functional protein coding transcript- CMPK2 and a previously identified type I IFN responsive lncRNA- NRIR. While these RNA are induced by virulent Mtb early, the complete absence of expression in non-viable Mtb infected cells coupled to a more protracted expression profile in the case of BCG suggest an important role in macrophage response to mycobacteria. Moreover, enhanced expression was observed in macrophages from TB patients. The elevated expression by 1h in response to fast growing bacteria further emphasizes the importance of these RNAs in the macrophage infection response. These transcripts (TILT1, 2,3 - T LR4 and I nfection induced L ong T ranscript) are triggered exclusively by TLR4 stimulation (LPS) with faster and stronger kinetics in comparison to the lncRNA – NRIR. Overall, we provide evidence for the presence of numerous transcripts that is a part of the early infection response program of macrophages.