Background
Tuberculosis is an international public health crisis, worsened by the COVID-19 pandemic
Tuberculosis (TB) is the leading cause of death from an infectious agent (mycobacterium tuberculosis; Mtb), killing 1.4 million people and making over 10 million people sick every year. The recent COVID-19 pandemic has killed over 6.5 million people worldwide and caused a TB syndemic.
NK cells can kill Mycobacterium tuberculosis (Mtb) but are tightly regulated.
NK cells are innate immune cells that play a protective role during Mtb infection by directly killing Mtb and lysing Mtb-infected cells. Their effector function, however, is tightly regulated by their expression of activating and inhibitory receptors.
CD49a + NK cells exist in the lung but their role during infection is yet to be defined.
Tissue-resident NK cell subsets, that express different receptors to those in the blood, populate the liver and the lung. We have shown that liver-resident NK cells have an enhanced ability to regulate CD8+ T cell activation yet the role of lung-resident NK cells is unknown. Lung NK cells express the integrin CD49a which has been shown to functionally differentiate skin-resident T cells into IFN-γ and IL-17 producers in the skin. We hypothesise that a similar dichotomy is at play in the lung with CD49a+ and CD49a- NK cells having distinct roles in the defence against TB.
Hypothesis:
CD49a+ and CD49a- lung NK cells have distinct immune responses against Mtb and their receptors can be targeted therapeutically to harness NK cell immunity against respiratory diseases such as TB.
Aim & Objectives:
To define how human lung resident NK cells respond to infection with Mtb.
1. Phenotype NK cells in human bronchoalveolar lavage (BAL) samples.
2. Investigate the role of CD49a in metabolism, cytokine production and cytotoxicity of BAL-NK cells in response to Mtb.
