MicroRNAs Contribute to Host Response to Coxiella burnetii, 2023, Sachan et al

[Hutan]

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.

https://pubmed.ncbi.nlm.nih.gov/36537791/

Also, see the PhD thesis:
https://pdxscholar.library.pdx.edu/cgi/viewcontent.cgi?article=6910&context=open_access_etds

 

[Hutan]

I was looking for something else and noticed that the miRNA found to be decreased during Coxiella burnetii infection was mir-143-3p. We've seen this miRNA before, in the 2014 Brenu paper on miRNA in ME/CFS. That paper identified three mRNA increased in ME/CFS, one of which was mir-143-3p.
High-Throughput Sequencing of Plasma MicroRNA in CFS/ME, 2014, Brenu, Staines, Marshall-Gradisnik et al

C. burnetii is of course the cause of Q-fever, and that can cause Q-fever fatigue syndrome, which is probably a type of ME/CFS.

 

[Hutan]

Interesting that the paper also mentions mir-142 - that was also found to be increased in ME/CFS by the Brenu paper:

For example, induction of miR-142-3p expression in macrophages leads to downregulation of N-Wasp, an actin-binding protein, resulting in reduced uptake of Mycobacterium tuberculosis (32).

We also demonstrate that transfecting host cells with miR-143-3p results in reduced C. burnetii growth, enhanced apoptosis and diminished autophagy. Collectively, our data indicate that an intracellular environment with a low level of miR-143-3p is conducive to C. burnetii growth.

In both cases, up-regulation of the two types of microRNA (as found in that 2014 ME/CFS study) might provide protection against a pathogen.

Together, our data suggest that lower levels of miR-143-3p present in C. burnetii-infected cells increases expression of akt1 and bcl2, which likely stalls apoptosis induction, thereby supporting the pathogen’s intracellular growth.

It would be great to have macrophages of people with Q-fever fatigue syndrome (and ME/CFS in general) tested for mir-142 levels. I'm not sure what hypothesis a confirmation of increased levels of mir-142 would lead to (a stale-mate with a latent infection? a response to an infection that hasn't turned off?), but knowing if there is a real difference would be a start.