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

Link to Article in PubMed

PubMed ID

32483198

Link to Full Text

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