ArticlePLoS pathogens2017
Engaging the CD40-CD40L pathway augments T-helper cell responses and improves control of Mycobacterium tuberculosis infection.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 73 citations in OpenAlex.
- Context-specific roles for IL-17 in tuberculosis.PLoS pathogens · 2026Review
- A CD40-OX40 co-stimulatory circuit orchestrates protective CD4Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Sex as a Biological Variable in Tuberculosis Pathogenesis.Immunological reviews · 2026Review
- T cell-macrophage interactions in tuberculosis: What we've got here is failure to communicate.Journal of internal medicine · 2026Review
- Cytotoxic granules and effector molecules from immune cells in tuberculosis: Mechanisms of host defense and therapeutic potential.Virulence · 2025Review
- Immunopathogenesis of tuberculosis: cellular mechanisms and immune modulation.Veterinary research · 2025Review
- Reprogrammed MDSCs promote Th1-dominant antitumour response via CD40 induced by autocrine TNF-α after combining cryo-thermal therapy with IL6 and IL17A neutralization.Clinical and translational medicine · 2025Article
- Using host and bacterial genetic approaches to define virulence strategies and protective immunity duringmSphere · 2025Review
- Alveolar macrophages from persons with HIV mount impaired TNF signaling networks to M. tuberculosis infection.Nature communications · 2025Article
- IFN-γ induced the formation of foamy macrophages via CD40 signal to controlFrontiers in immunology · 2025Article
- The diagnostic value and validation of IL-22 combimed with sCD40L in tuberculosis pleural effusion.BMC immunology · 2024Article
- Vaccination with Mincle agonist UM-1098 and mycobacterial antigens induces protective Th1 and Th17 responses.NPJ vaccines · 2024Article
- From pathogenesis to antigens: the key to shaping the future of TB vaccines.Frontiers in immunology · 2024Review
- From immunology to artificial intelligence: revolutionizing latent tuberculosis infection diagnosis with machine learning.Military Medical Research · 2023Review
- OMIP-096: A 24-color flow cytometry panel to identify and characterize CD4+ and CD8+ tissue-resident T cells in human skin, intestinal, and type II mucosal tissue.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2023Article
- TB granuloma: CD30 co-stimulation for CD4+ T cell co-operation.The Journal of experimental medicine · 2023Article
- Blood monocyte and dendritic cell profiles among people living with HIV with Mycobacterium tuberculosis co-infection.BMC immunology · 2023Article
- Blocking CD40 Alleviates Th1 and Th17 Cell Responses in Elastin Peptide-Induced Murine Emphysema.International journal of chronic obstructive pulmonary disease · 2023Article
- Glucose metabolism and its role in the maturation and migration of human CD1cFrontiers in cellular and infection microbiology · 2023Article
- Tuberculosis dissemination in kidney transplant recipient treated with anti-CD40 monoclonal antibody: a case report.BMC nephrology · 2022Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Mycobacterium tuberculosis (Mtb) impairs dendritic cell (DC) functions and induces suboptimal antigen-specific CD4 T cell immune responses that are poorly protective. Mucosal T-helper cells producing IFN-γ (Th1) and IL-17 (Th17) are important for protecting against tuberculosis (TB), but the mechanisms by which DCs generate antigen-specific T-helper responses during Mtb infection are not well defined. We previously reported that Mtb impairs CD40 expression on DCs and restricts Th1 and Th17 responses. We now demonstrate that CD40-dependent costimulation is required to generate IL-17 responses to Mtb. CD40-deficient DCs were unable to induce antigen-specific IL-17 responses after Mtb infection despite the production of Th17-polarizing innate cytokines. Disrupting the interaction between CD40 on DCs and its ligand CD40L on antigen-specific CD4 T cells, genetically or via antibody blockade, significantly reduced antigen-specific IL-17 responses. Importantly, engaging CD40 on DCs with a multimeric CD40 agonist (CD40LT) enhanced antigen-specific IL-17 generation in ex vivo DC-T cell co-culture assays. Further, intratracheal instillation of Mtb-infected DCs treated with CD40LT significantly augmented antigen-specific Th17 responses in vivo in the lungs and lung-draining lymph nodes of mice. Finally, we show that boosting CD40-CD40L interactions promoted balanced Th1/Th17 responses in a setting of mucosal DC transfer, and conferred enhanced control of lung bacterial burdens following aerosol challenge with Mtb. Our results demonstrate that CD40 costimulation by DCs plays an important role in generating antigen-specific Th17 cells and targeting the CD40-CD40L pathway represents a novel strategy to improve adaptive immunity to TB.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.