Our Research
Tuberculosis (TB), the disease caused by the pathogen Mycobacterium tuberculosis (Mtb) remains a global public health burden. Approximately 10 million people across the world become newly infected with Mtb and nearly 1.5 million people die from TB. There is currently no effective vaccine that prevents disease and antibiotic resistance complicates therapy. We use immunological approaches to find novel solutions to combat TB.
Research
in Focus
Antibodies are a powerful and adaptive feature of the immune response to infection that can coordinate potent protection against pathogens. The Grace lab studies antibody Fc effector functions that result from antibody constant domain (Fc) interactions with Fc Receptors (FcR) on cells of the immune system. We hypothesize that rationally selected Fc-functions delivered to the immune system can improve Mtb infection and disease outcomes.
We use systems approaches to understand antibody-mediated immunity in patients with TB. We model this immunity with monoclonal antibodies applying them to human and animal models of Mtb infection.
Fc-mediated immune responses are tightly regulated during infection, and antibody isotype, subclass, and Fc-glycosylation shift throughout infection to tune the antibody-Fc affinity for FcRs which in turn tunes the functional output that arises from the Fc-FcR interaction on immune cells. We profile the antibody responses to TB Infection and vaccination with the goal of linking specific antibody features to disease outcome. The correlates we identify in patients inspire our mechanistic studies of antibodies.
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How antibodies signal to the immune system during Mtb infection to elicit immune control in vivo is unknown. Phagocytes express a diversity of FcRs and likely integrate Fc-mediated signals to induce inflammatory, immunomodulatory, or bacterially restrictive responses within a cell. Our research aims to uncover how Fc-mediated signals modulate cellular immunity in the lung to restrict or permit bacterial growth in vivo.
02.
Via FcR interactions on dendritic cells, antibodies can promote enhanced antigen presentation that enhances T cell responses to infection. We are investigating the role of Fc-mediated function in T cell priming and activation during Mtb infection. Antibody-mediated signals may improve T cell recognition of infected cells promoting better infection control.
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Read more about our research
The approaches and tools we use to investigate TB immunity can be applied to study other pathogens of the lung and beyond. We are always interested in incorporating novel approaches to understand TB immunity.
Connect with us about potential collaborations!
