Specificity of the innate immune responses to different classes of non-tuberculous mycobacteria

Front Immunol. 2023 Jan 18:13:1075473. doi: 10.3389/fimmu.2022.1075473. eCollection 2022.

Abstract

Mycobacterium avium is the most common nontuberculous mycobacterium (NTM) species causing infectious disease. Here, we characterized a M. avium infection model in zebrafish larvae, and compared it to M. marinum infection, a model of tuberculosis. M. avium bacteria are efficiently phagocytosed and frequently induce granuloma-like structures in zebrafish larvae. Although macrophages can respond to both mycobacterial infections, their migration speed is faster in infections caused by M. marinum. Tlr2 is conservatively involved in most aspects of the defense against both mycobacterial infections. However, Tlr2 has a function in the migration speed of macrophages and neutrophils to infection sites with M. marinum that is not observed with M. avium. Using RNAseq analysis, we found a distinct transcriptome response in cytokine-cytokine receptor interaction for M. avium and M. marinum infection. In addition, we found differences in gene expression in metabolic pathways, phagosome formation, matrix remodeling, and apoptosis in response to these mycobacterial infections. In conclusion, we characterized a new M. avium infection model in zebrafish that can be further used in studying pathological mechanisms for NTM-caused diseases.

Keywords: Tlr2; leukocyte migration; metabolism; nontuberculous mycobacterium; zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Immunity, Innate
  • Larva
  • Mycobacterium Infections, Nontuberculous*
  • Nontuberculous Mycobacteria*
  • Toll-Like Receptor 2
  • Zebrafish

Substances

  • Toll-Like Receptor 2

Grants and funding

This work was supported by a grant from the Innovative Medicines Initiative 2 Joint Undertaking (IMI2 JU) under the RespiriNTM project (Grant No. 853932).