Concerns of severe flu cases consist of every a lowered and an increased choice of platelets in the blood, which shall be related to an increased likelihood of thrombosis. Researchers led by Professor Ute Modlich, head of the learn team “Gene Modification in Stem Cells” at the Paul-Ehrlich-Institut, bear labored in a learn community with scientists at the German Cancer Study Centre (DKFZ) Heidelberg and the College of Heidelberg on the connection between a flu virus infection (H1N1) and the formation of blood or platelets. H1N1 influenza viruses are among the influenza viruses that circulation every yr in Germany.
An infection of the lungs with influenza viruses and its impact on blood formation
All blood cells and thus also all platelets are renewed by stem cells that can well originate into blood cells (hematopoietic stem cells, HSCs). These cells exist in a resting whisper in the bone marrow. The fate of the HSCs is strictly regulated between rest, self-renewal and differentiation in characterize to originate constructive lifelong hematopoiesis.
In characterize to investigate the impact of influenza infection on blood formation, mice were contaminated intranasally with influenza viruses and their blood stem cells were attributable to this truth investigated with regards to differentiation and cell cycle activation. Within the first three days of acute influenza infection, the platelets at the origin diminished (thrombocytopenia), but then rose immediately in the blood to ranges above physiological ranges (thrombocytosis). These immediately produced platelets had an immature look (phenotype) and were more immediately activatable (hyper-reactive).
An increased choice of blood stem cells were uncover in the maturation route of unprejudiced two days after infection (G1 and S/G2/M cell cycle section). The activation of the blood stem cells correlated positively with the viral lung titer, i.e., the more viruses had attacked the lungs, the more blood stem cells were activated. Infections with lowered influenza doses delayed stem cell activation, but could well well now no longer prevent it. Within the regeneration section, the blood stem cells returned to the resting section. This occurred quicker in vaccinated mice than in various groups.
Blood stem cells with conventional markers for platelet precursors
In characterize to elaborate the quiz of how platelets could well well be produced so instant, the learn crew took a more in-depth think about at the phenotype of the activated blood stem cells and discovered that a subset of the blood stem cells already carried conventional markers of platelet precursor cells (megakaryocytes). Blood stem cells with this ground phenotype differentiate at once into megakaryocytes and get platelets. They skip a couple of preceding levels. The learn team demonstrated through in vitro lineage tracing and bone marrow transplants that this team of blood stem cells immediately multiply in the bone marrow after influenza infection. These newly produced platelets are larger and more immature in look than trendy platelets and are inclined to set off more immediately, which will outcome in a larger menace of blood clots in the lungs.
The strategy of snappy differentiation of megakaryocytes has indeed already been described as emergency megakaryopoiesis, which occurs constant with systemic inflammations or infections. To this point, nonetheless, no affiliation with local viral respiratory diseases has been suspected. Despite the truth that the influenza virus infection in mice became restricted to the respiratory tract, increased ranges of the cytokines interleukin-1 (IL-1) and interleukin-6 (IL-6) were uncover in the bone marrow of contaminated mice. The use of two groups of knockout mice, one with the IL-1 receptor switched off and one with the IL-6 receptor switched off, the learn team demonstrated that these cytokines contribute decisively to the activation of the blood stem cells and to emergency megakaryopoiesis in influenza infections.
The hot knowledge worth that even a local (non-systemic) viral infection can outcome in changes in blood formation in the bone marrow. Platelets formed in this route of can outcome in a larger menace of blood clots, severely in the lungs, in the hyper-reactive whisper. This would well bear a predominant impact on staunch flu cases.
Extra knowledge:
Marcel G.E. Rommel et al, Influenza A pandemic infection instructs hematopoiesis to megakaryocyte-lineage output, Cell Experiences (2022). DOI: 10.1016/j.celrep.2022.111447
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The influenza virus and its impact on blood stem cells and coagulation (2022, October 18)
retrieved 18 October 2022
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