Journal de bioterrorisme et de biodéfense

Abstrait

Transcriptional Profiling of Human Peripheral Blood Mononuclear Cells Exposed to Bacillus anthracis in vitro

Rasha Hammamieh, Nabarun Chakraborty, Mohsen Barmada, Matthew Hellman, Seid Muhie, James Koterski, Rina Das3 and Marti Jett

Dependable and efficient diagnosis of Bacillus anthracis has long been a major concern for caregivers. Nonspecific symptoms during early illness often misguide the diagnosis; thereby jeopardize the proper therapeutic intervention. It is, therefore, crucial to understand the initial events that take place in a host soon after the onset of infection. The present study examines the transcriptional profile of human peripheral blood mononuclear cells (PBMCs) challenged by B. anthracis (BA) spores in vitro, and cultured for 2 hrs, 4hrs, 6 hrs, 8 hrs and 24 hrs, respectively. Transcriptomic assays support the past findings and identify novel targets for diagnosis and anthrax therapy. We observe rapid elevation of a number of transcripts encoding genes for cytokines, chemokines, and other uptake receptors, concurrently with onset of infection. Delayed responses to the BA include gradual attenuation of the genes linked with pathogenic uptake, such as MyD88 and TLR4, putatively extending the duration of host vulnerability. The signs of altering host defenses, nevertheless are evident immediately after the exposure to the B. anthracis spores. The pathogenic insult selectively induces some of the key genes for apoptotic pathways regulated by the toll-like receptors and the caspase cascade; and suppresses the transcripts related to the p38MAPK-dependent pathways. The T-cell receptors and CD3-mediated antigenic recognition processes are possibly restrained, and the expression of CD79, a B-cell committed CD marker, is suppressed. Overall, BA challenges both innate and adaptive immunity processes and their key interfaces during the early course of infection. We identified several early targets across the networks and pathways, primarily related to chemotaxis and apoptosis of immune cells that can potentially facilitate development of next generation anthrax prevention strategies.