Granulocytes act as a niche for Mycobacterium tuberculosis growth.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Lovewell, RR; Baer, CE; Mishra, BB; Smith, CM; Sassetti, CM

Published Date

  • January 2021

Published In

Volume / Issue

  • 14 / 1

Start / End Page

  • 229 - 241

PubMed ID

  • 32483198

Pubmed Central ID

  • PMC7704924

Electronic International Standard Serial Number (EISSN)

  • 1935-3456

Digital Object Identifier (DOI)

  • 10.1038/s41385-020-0300-z

Language

  • eng

Conference Location

  • United States