Biology subjects

Plumlee, C. R.

Publications and source records attributed to Plumlee, C. R..

2 recordsLinked to original sources

bioRxiv2019

TGFβ restricts T cell function and bacterial control within the tuberculous granuloma

Interferon gamma (IFN{gamma}) produced by CD4 T cells is required for immune containment of Mycobacterium tuberculosis (Mtb) infection. Despite this, IFN{gamma} plays a minor role in CD4 T cell-mediated immunity within the lung. In this study, we use a recently-developed murine model of physiologic Mtb infection coupled with advanced quantitative imaging to demonstrate that IFN{gamma} production by Mtb-specific T cells is rapidly extinguished within the granuloma, but not in unaffected areas of the lung. This is mediated via localized immunosuppression through cell-intrinsic TGF{beta} signaling in effector T helper 1 cells within the granuloma, and blockade of TGF{beta} signaling in T cells results in improved immune cell function and decreased pulmonary bacterial burden. These findings uncover a potent immunosuppressive mechanism associated with Mtb infection and provide potential targets for host-directed therapy.

immunology↗

bioRxiv2019

BCG-induced T cells shape Mycobacterium tuberculosis infection before reducing the bacterial burden

Growing evidence suggests the outcome of Mycobacterium tuberculosis (Mtb) infection is established rapidly after exposure, but how the current tuberculosis vaccine, BCG, impacts early immunity is poorly understood. Here we found that murine BCG immunization promotes a dramatic shift in infected cell types. While alveolar macrophages (AM) are the major infected cell for the first two weeks in unimmunized animals, BCG promotes the accelerated recruitment and infection of lung infiltrating phagocytes. Interestingly, this shift is dependent on CD4 T cells, yet does not require intrinsic recognition of antigen presented by infected AM. Mtb-specific T cells are first activated in lung regions devoid of infected cells, and these events precede vaccine-induced reduction of the bacterial burden, which occurs only after the co-localization of T cells and infected cells. Understanding how BCG alters early immune responses to Mtb provides new avenues to improve upon the immunity it confers.

immunology↗