Alveolar macrophages (AMs) are innate sentinels of the lungs and are the first immune cells to encounter inhaled pathogens. During infection with Mycobacterium tuberculosis (Mtb), AMs phagocytose Mtb and are the only cells productively infected for the first 14 days. I hypothesize the initial response of AMs may influence disease progression and outcomes. Specifically, I have investigated the production of interferon beta (IFN-β) since previous studies have shown that patients with active tuberculosis had blood transcriptional profiles dominated by a Type I IFN-inducible gene signature. I have used B16 IFN-⍺/β reporter cells to measure macrophage production of Type I IFNs in response to stimulation with a variety of pathogen associated molecular patterns. I have found that AMs consistently produce less bioactive IFN-β than macrophages derived from the bone marrow across a variety of different pathogen patterns. However, surprisingly, AMs produce more IFN-β than BMDMs when treated with recombinant IFN-β. As such, it seems that the IFN-β positive feedback loop differs between these two cell types. My ongoing research is further investigating the regulation of this feedback loop. 

This research delves into the understudied role of innate immunity during the early days of infection. Mtb causes tuberculosis, a disease impacting nearly 1 in 4 people. Although a vaccine is available, the current BCG vaccine is only effective in children and provides limited protection. By investigating how the innate immune responses is regulated during the early stages of infection we may begin to uncover better preventative strategies or therapies to fight tuberculosis.