Title
Granulocytes act as a niche for Mycobacterium tuberculosis growth
UMMS Affiliation
Department of Microbiology and Physiological Systems
Publication Date
2021-01-01
Document Type
Article
Disciplines
Bacteria | Bacterial Infections and Mycoses | Bacteriology | Immunology and Infectious Disease
Abstract
Granulocyte recruitment to the pulmonary compartment is a hallmark of progressive tuberculosis (TB). This process is well-documented to promote immunopathology, but can also enhance the replication of the pathogen. Both the specific granulocytes responsible for increasing mycobacterial burden and the underlying mechanisms remain obscure. We report that the known immunomodulatory effects of these cells, such as suppression of protective T-cell responses, play a limited role in altering host control of mycobacterial replication in susceptible mice. Instead, we find that the adaptive immune response preferentially restricts the burden of bacteria within monocytes and macrophages compared to granulocytes. Specifically, mycobacteria within inflammatory lesions are preferentially found within long-lived granulocytes that express intermediate levels of the Ly6G marker and low levels of antimicrobial genes. These cells progressively accumulate in the lung and correlate with bacterial load and disease severity, and the ablation of Ly6G-expressing cells lowers mycobacterial burden. These observations suggest a model in which dysregulated granulocytic influx promotes disease by creating a permissive intracellular niche for mycobacterial growth and persistence.
Keywords
tuberculosis, TB, granulocytes, mycobacteria
DOI of Published Version
10.1038/s41385-020-0300-z
Source
Lovewell RR, Baer CE, Mishra BB, Smith CM, Sassetti CM. Granulocytes act as a niche for Mycobacterium tuberculosis growth. Mucosal Immunol. 2021 Jan;14(1):229-241. doi: 10.1038/s41385-020-0300-z. Epub 2020 Jun 1. PMID: 32483198; PMCID: PMC7704924. Link to article on publisher's site
Journal/Book/Conference Title
Mucosal immunology
Related Resources
PubMed ID
32483198
Repository Citation
Lovewell RR, Baer CE, Mishra BB, Smith CM, Sassetti CM. (2021). Granulocytes act as a niche for Mycobacterium tuberculosis growth. Open Access Publications by UMMS Authors. https://doi.org/10.1038/s41385-020-0300-z. Retrieved from https://escholarship.umassmed.edu/oapubs/4558