Review Recent Advances on the Innate Immune Response to Coxiella burnetii, 2021, Sireci et al

Recent Advances on the Innate Immune Response to Coxiella burnetii
Guido Sireci, 1 Giusto Davide Badami, 1 Diana Di Liberto, 1 Valeria Blanda, 2 , * Francesca Grippi, 2 Laura Di Paola, 2Annalisa Guercio, 2 José de la Fuente, 3 , 4 and Alessandra Torina 2

Abstract
Coxiella burnetii is an obligate intracellular Gram-negative bacterium and the causative agent of a worldwide zoonosis known as Q fever. The pathogen invades monocytes and macrophages, replicating within acidic phagolysosomes and evading host defenses through different immune evasion strategies that are mainly associated with the structure of its lipopolysaccharide. The main transmission routes are aerosols and ingestion of fomites from infected animals. The innate immune system provides the first host defense against the microorganism, and it is crucial to direct the infection towards a self-limiting respiratory disease or the chronic form.

This review reports the advances in understanding the mechanisms of innate immunity acting during C. burnetii infection and the strategies that pathogen put in place to infect the host cells and to modify the expression of specific host cell genes in order to subvert cellular processes. The mechanisms through which different cell types with different genetic backgrounds are differently susceptible to C. burnetii intracellular growth are discussed. The subsets of cytokines induced following C. burnetii infection as well as the pathogen influence on an inflammasome-mediated response are also described.

Finally, we discuss the use of animal experimental systems for studying the innate immune response against C. burnetii and discovering novel methods for prevention and treatment of disease in humans and livestock.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593175/

 

I'm part the way through this relatively recent review paper, and I'm finding it interesting, especially in the light of recent findings from Long Covid studies, such as the possibility that interferons and infected monocytes play a role in post-infection syndromes.

I think the fact that so many of the infections that seem to trigger ME/CFS-like disease have been shown to be able to persist in cells is a clue.

C. burnetii has two forms, the small cell variant and the large cell variant. The small cell variant can exist in an acidic lysosome in a cell, with genes activated that reduce cell wall shedding, to reduce its detection by immune detectors inside the cell.


C. burnetii also varies in the nature of its cell wall (LPS) - there's a reference to phase 1 and phase 2 versions. The difference seems to be important for chronicity. I'm not fully understanding when and where these phases come into play and the consequences of each.

This 1998 finding of increased IFN-y in people with QFS seems important, given the recent finding of this in a subset of people with post-Covid symptoms:

Here's a comment on the Raijmaker paper about the possibility of an infection causing epigenetic remodelling relevant to QFS:

 

On interferons:

It is reported that IFN-y levels are not increased in chronic Q-fever patients, and that 'QFS patients showed similar levels of IFN-y' as those affected by chronic Q fever. So those two reported facts suggests that IFN-y levels are not higher in QFS than in healthy people - which is different to what was reported just above from the 1998 paper. I guess it would be necessary to go to the original papers and check.

Type 1 interferons are discussed but not in the context of QFS:

 

On apoptosis:

That suggests the bacteria can infect neutrophils in bone marrow and extend the life of the host cells.

There's a couple of references given for the existence of QFS as a thing:

and some comment on the persistence of Coxiella cell components long after an acute infection that are able to induce an abnormal immune response: