CD4+ T cells re-wire granuloma cellularity and regulatory networks to promote immunomodulation following Mtb reinfection
Year: 2024
Type: article
Abstract: Immunological priming—in the context of either prior infection or vaccination—elicits protective responses against subsequent Mycobacterium tuberculosis ( Mtb ) infection. However, the changes that occur in the lung cellular milieu post-primary Mtb infection and their contributions to protection upon reinfection remain poorly understood. Using clinical and microbiological endpoints in a non-human primate reinfection model, we demonstrated that prior Mtb infection elicited a long-lasting protective response against subsequent Mtb exposure and was CD4 + T cell dependent. By analyzing data from primary infection, reinfection, and reinfection-CD4 + T cell-depleted granulomas, we found that the presence of CD4 + T cells during reinfection resulted in a less inflammatory lung milieu characterized by reprogrammed CD8 + T cells, reduced neutrophilia, and blunted type 1 immune signaling among myeloid cells. These results open avenues for developing vaccines and therapeutics that not only target lymphocytes but also modulate innate immune cells to limit tuberculosis (TB) disease.
Source: Immunity
Authors: Joshua D. Bromley, Sharie Keanne C. Ganchua, Sarah K. Nyquist, Pauline Maiello, Michael Chao, H. Jacob Borish, Mark Rodgers, Jaime Tomko, Kara Kracinovsky, Douaa Mugahid, Son Nguyen, Qianchang Dennis Wang, Jacob M. Rosenberg, Edwin C. Klein, Hannah P. Gideon, Roisin Floyd-O’Sullivan, Bonnie Berger, Charles A. Scanga, Philana Ling Lin, Sarah M. Fortune, Alex K. Shalek, JoAnne L. Flynn
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $9,350
Funders: Bill and Melinda Gates Foundation, Harvard University, Harvard University Center for AIDS Research, Harvard Catalyst, University of Pittsburgh, National Institutes of Health, Center for AIDS Research, University of Washington, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences, Office of Research Infrastructure Programs, National Institutes of Health
Awards: G1575283533, G1722716446, Graduate Training in Computational and Systems Biology, Institutional Career Development Core, G2115375026, The General Hospital Corporation d/b/a Massachusetts General Hospital - to increase the actionable knowledge gained from single-cell genomic data sets by improving data access and creating user-friendly analytical tools..., G2833012269, G345173699, G4955885207, G6811973346, G7578466963, The Consequences of Reinfection with M. tuberculosis, G7785852513, G8926664050, Pitt RBL, Nonhuman Primate Antibody Resource for Immune Cell Depletion, Multidisciplinary HIV Training Program, Harvard University Center for AIDS Research, Nonhuman Primate Reagent Resource
OpenAlex ID: W4401992140