Phospholipase C epsilon-1 (PLCƐ1) mediates macrophage activation and protection against tuberculosis
Year: 2024
Type: article
Abstract: ABSTRACT Tuberculosis (TB) caused by Mycobacterium tuberculosis ( Mtb ) infects up to a quarter of the world’s population. Although immune responses can control Mtb infection, 5%–10% of infected individuals can progress to active TB disease (progressors). A myriad of host factors regulate disease progression in TB and a better understanding of immune correlates of protection and disease is pivotal for the development of new therapeutics. Comparison of human whole blood transcriptomic metadata with that of macaque TB progressors and Mtb -infected diversity outbred mice (DO) led to the identification of differentially regulated gene (DEG) signatures, associated with TB progression or control. The current study assessed the function of Phospholipase C epsilon ( PLCƐ1 ), the top downregulated gene across species in TB progressors, using a gene-specific knockout mouse model of Mtb infection and in vitro Mtb -infected bone marrow-derived macrophages. PLCƐ1 gene expression was downregulated in TB progressors across species. PLCε1 deficiency in the mouse model resulted in increased susceptibility to Mtb infection , coincident accumulation of lung myeloid cells, and reduced ability to mount antibacterial responses. However, PLCε1 was not required for the activation and accumulation of T cells in mice. Our results suggest an important early role for PLCƐ1 in shaping innate immune response to TB and may represent a putative target for host-directed therapy.
Source: Infection and Immunity
DOI: 10.1128/iai.00495-23
Institutions: University of Chicago, Washington University in St. Louis, University of Rochester Medicine, University of Rochester, University of Cape Town, South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, University of Michigan, Texas Biomedical Research Institute
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: The Role of Group 3 Innate Lymphoid cells (ILC3) in Tuberculosis, Novel IL-17 producing memory cells are key to vaccine-based immunity in the lung, COMMON IMMUNE CORRELATES OF RISK OF TB DISEASE IN ANIMAL MODELS AND HUMANS, G9000139771, Role of Inducible Bronchus Associated Lymphoid Tissue in Latent Tuberculosis, The Southwest National Primate Research Center, Role of IL-17 in Protective Vaccine-induced Immune Responses Against Tuberculosis, Understanding and Manipulating G Protein α Subunit and Phospholipase C Signaling Networks
OpenAlex ID: W4392561797