MicroRNAs Contribute to Host Response to Coxiella burnetii

Infect Immun. 2023 Jan 24;91(1):e0019922. doi: 10.1128/iai.00199-22. Epub 2022 Dec 20.

Abstract

MicroRNAs (miRNAs), a class of small noncoding RNAs, are critical to gene regulation in eukaryotes. They are involved in modulating a variety of physiological processes, including the host response to intracellular infections. Little is known about miRNA functions during infection by Coxiella burnetii, the causative agent of human Q fever. This bacterial pathogen establishes a large replicative vacuole within macrophages by manipulating host processes such as apoptosis and autophagy. We investigated miRNA expression in C. burnetii-infected macrophages and identified several miRNAs that were down- or upregulated during infection. We further explored the functions of miR-143-3p, an miRNA whose expression is downregulated in macrophages infected with C. burnetii, and show that increasing the abundance of this miRNA in human cells results in increased apoptosis and reduced autophagy-conditions that are unfavorable to C. burnetii intracellular growth. In sum, this study demonstrates that C. burnetii infection elicits a robust miRNA-based host response, and because miR-143-3p promotes apoptosis and inhibits autophagy, downregulation of miR-143-3p expression during C. burnetii infection likely benefits the pathogen.

Keywords: Coxiella burnetii; apoptosis; autophagy; infection; macrophage; miRNA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Coxiella burnetii* / physiology
  • Host-Pathogen Interactions / genetics
  • Humans
  • Macrophages / microbiology
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Q Fever* / genetics
  • Q Fever* / metabolism
  • Vacuoles / microbiology

Substances

  • MicroRNAs