Friday, September 18, 2015

Gut microbiota controls clinical severity of sickle-cell disease via neutrophil "ageing"

Our knowledge of the role of gut microbiome in human health and disease is expanding on a daily basis.

For example, just few days ago journal Nature published a study where the authors showed that in mouse model of sickle-cell disease (Hba-/- Hbb -/-) the presence gut microbiome influenced clinical severity via neutrophil "ageing".      

In sickle-cell disease, neutrophils expressing Mac-1 capture sickle red blood cells that leads to vaso-occlusion and tissue damage. It appears that "ageing", or mature neutrophils, defined as CD62Llow CXCR4high population, express more Mac-1 and those neutrophils can capture more RBCs per cell basis (that contributes to development of sickle-cell disease symptoms). [the authors does not discuss the difference between "ageing", "senescence" and "mature" neutrophils].

Next, the authors showed that germ-free mice or antibiotic treated mice have reduced number of "ageing" neutrophils.

Using BM chimera, the authors found that absence of MyD88 adaptor molecule or TLR4 receptor also mimicked the effect of antibiotic treatment on neutrophil "ageing".

Finally, the authors found that antibiotic treatment of sickle-cell disease model mice reduced number of circulating "ageing" Mac-1 expressing neutrophils and showed reduction in tissue damage.

In summary, this study proposed a novel therapeutic path for treatment for sickle-cell disease by modulation of gut microbiota and neutrophil maturation ("ageing").

David Usharauli

No comments:

Post a Comment