5 documents found, page 1 of 1
IL-21 signaling is essential for optimal host resistance against Mycobacterium ...
Booty, Matthew G.; Silva, Palmira Conceição Araújo Barreira; Carpenter, Stephen M.; Nunes-Alves, Cláudio; Jacques, Miye K.; Stowell, Britni L.IL-21 is produced predominantly by activated CD4(+) T cells and has pleiotropic effects on immunity via the IL-21 receptor (IL-21R), a member of the common gamma chain (gamma(c)) cytokine receptor family. We show that IL-21 signaling plays a crucial role in T cell responses during Mycobacterium tuberculosis infection by augmenting CD8(+) T cell priming, promoting T cell accumulation in the lungs, and enhancing ...
A higher activation threshold of memory CD8+ T cells has a fitness cost that is...
Carpenter, Stephen M; Nunes-Alves, Cláudio; Booty, Matthew G; Way, Sing Sing; Behar, Samuel MT cell vaccines against Mycobacterium tuberculosis (Mtb) and other pathogens are based on the principle that memory T cells rapidly generate effector responses upon challenge, leading to pathogen clearance. Despite eliciting a robust memory CD8+ T cell response to the immunodominant Mtb antigen TB10.4 (EsxH), we find the increased frequency of TB10.4-specific CD8+ T cells conferred by vaccination to be short-li...
In search of a new paradigm for protective immunity to TB
Nunes-Alves, Cláudio; Booty, Matthew G.; Carpenter, Stephen M.; Jayaraman, Pushpa; Rothchild, Alissa C.; Behar, Samuel M.Clinical trials of vaccines against Mycobacterium tuberculosis are well under way and results are starting to come in. Some of these results are not so encouraging, as exemplified by the latest Aeras-422 and MVA85A trials. Other than empirically determining whether a vaccine reduces the number of cases of active tuberculosis, which is a daunting prospect given the chronic nature of the disease, we have no way o...
Efferocytosis is an innate antibacterial mechanism
Martin, Constance J.; Booty, Matthew G.; Rosebrock, Tracy R.; Nunes-Alves, Cláudio; Desjardins, Danielle M.; Keren, Iris; Fortune, Sarah M.Mycobacterium tuberculosis persists within macrophages in an arrested phagosome and depends upon necrosis to elude immunity and disseminate. Although apoptosis of M. tuberculosis-infected macrophages is associated with reduced bacterial growth, the bacteria are relatively resistant to other forms of death, leaving the mechanism underlying this observation unresolved. We find that after apoptosis, M. tuberculosi...
Dissemination of mycobacteria to the thymus renders newly generated T cells tol...
Nobrega, Claudia; Roque, Susana; Nunes-Alves, Cláudio; Coelho, Angela; Medeiros, Irene; Castro, António G.; Appelberg, Rui; Correia-Neves, MThe ability of the thymus to generate a population of T cells that is, for the most part, self-restricted and self-tolerant depends to a great extent on the Ags encountered during differentiation. We recently showed that mycobacteria disseminate to the thymus, which raised the questions of how mycobacteria within the thymus influence T cell differentiation and whether such an effect impacts host-pathogen intera...