Microtubules and Dynein Regulate Human Neutrophil Nuclear Volume and Hypersegmentation During H. pylori Infection
Neutrophils (also called polymorphonuclear leukocytes, PMNs) are heterogeneous and can exhibit considerable phenotypic and functional plasticity. In keeping with this, we discovered previously that Helicobacter pylori infection induces N1-like subtype differentiation of human PMNs that is notable fo...
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doaj-59ca118100274fa2b61127e6e7883b5d2021-03-22T04:22:52ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-03-011210.3389/fimmu.2021.653100653100Microtubules and Dynein Regulate Human Neutrophil Nuclear Volume and Hypersegmentation During H. pylori InfectionStephanie L. Silva-Del Toro0Stephanie L. Silva-Del Toro1Lee-Ann H. Allen2Lee-Ann H. Allen3Lee-Ann H. Allen4Lee-Ann H. Allen5Lee-Ann H. Allen6Inflammation Program of the University of Iowa, Iowa City, IA, United StatesImmunology Graduate Program of the University of Iowa, Iowa City, IA, United StatesInflammation Program of the University of Iowa, Iowa City, IA, United StatesImmunology Graduate Program of the University of Iowa, Iowa City, IA, United StatesDepartment of Internal Medicine, University of Iowa, Iowa City, IA, United StatesDepartment of Microbiology and Immunology, University of Iowa, Iowa City, IA, United StatesIowa City VA Healthcare System, Iowa City, IA, United StatesNeutrophils (also called polymorphonuclear leukocytes, PMNs) are heterogeneous and can exhibit considerable phenotypic and functional plasticity. In keeping with this, we discovered previously that Helicobacter pylori infection induces N1-like subtype differentiation of human PMNs that is notable for profound nuclear hypersegmentation. Herein, we utilized biochemical approaches and confocal and super-resolution microscopy to gain insight into the underlying molecular mechanisms. Sensitivity to inhibition by nocodazole and taxol indicated that microtubule dynamics were required to induce and sustain hypersegmentation, and super-resolution Stimulated Emission Depletion (STED) imaging demonstrated that microtubules were significantly more abundant and longer in hypersegmented cells. Dynein activity was also required, and enrichment of this motor protein at the nuclear periphery was enhanced following H. pylori infection. In contrast, centrosome splitting did not occur, and lamin B receptor abundance and ER morphology were unchanged. Finally, analysis of STED image stacks using Imaris software revealed that nuclear volume increased markedly prior to the onset of hypersegmentation and that nuclear size was differentially modulated by nocodazole and taxol in the presence and absence of infection. Taken together, our data define a new mechanism of hypersegmentation that is mediated by microtubules and dynein and as such advance understanding of processes that regulate nuclear morphology.https://www.frontiersin.org/articles/10.3389/fimmu.2021.653100/fullneutrophilsplasticityhypersegmentationmicrotubulesdyneinlamin B receptor |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Stephanie L. Silva-Del Toro Stephanie L. Silva-Del Toro Lee-Ann H. Allen Lee-Ann H. Allen Lee-Ann H. Allen Lee-Ann H. Allen Lee-Ann H. Allen |
spellingShingle |
Stephanie L. Silva-Del Toro Stephanie L. Silva-Del Toro Lee-Ann H. Allen Lee-Ann H. Allen Lee-Ann H. Allen Lee-Ann H. Allen Lee-Ann H. Allen Microtubules and Dynein Regulate Human Neutrophil Nuclear Volume and Hypersegmentation During H. pylori Infection Frontiers in Immunology neutrophils plasticity hypersegmentation microtubules dynein lamin B receptor |
author_facet |
Stephanie L. Silva-Del Toro Stephanie L. Silva-Del Toro Lee-Ann H. Allen Lee-Ann H. Allen Lee-Ann H. Allen Lee-Ann H. Allen Lee-Ann H. Allen |
author_sort |
Stephanie L. Silva-Del Toro |
title |
Microtubules and Dynein Regulate Human Neutrophil Nuclear Volume and Hypersegmentation During H. pylori Infection |
title_short |
Microtubules and Dynein Regulate Human Neutrophil Nuclear Volume and Hypersegmentation During H. pylori Infection |
title_full |
Microtubules and Dynein Regulate Human Neutrophil Nuclear Volume and Hypersegmentation During H. pylori Infection |
title_fullStr |
Microtubules and Dynein Regulate Human Neutrophil Nuclear Volume and Hypersegmentation During H. pylori Infection |
title_full_unstemmed |
Microtubules and Dynein Regulate Human Neutrophil Nuclear Volume and Hypersegmentation During H. pylori Infection |
title_sort |
microtubules and dynein regulate human neutrophil nuclear volume and hypersegmentation during h. pylori infection |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2021-03-01 |
description |
Neutrophils (also called polymorphonuclear leukocytes, PMNs) are heterogeneous and can exhibit considerable phenotypic and functional plasticity. In keeping with this, we discovered previously that Helicobacter pylori infection induces N1-like subtype differentiation of human PMNs that is notable for profound nuclear hypersegmentation. Herein, we utilized biochemical approaches and confocal and super-resolution microscopy to gain insight into the underlying molecular mechanisms. Sensitivity to inhibition by nocodazole and taxol indicated that microtubule dynamics were required to induce and sustain hypersegmentation, and super-resolution Stimulated Emission Depletion (STED) imaging demonstrated that microtubules were significantly more abundant and longer in hypersegmented cells. Dynein activity was also required, and enrichment of this motor protein at the nuclear periphery was enhanced following H. pylori infection. In contrast, centrosome splitting did not occur, and lamin B receptor abundance and ER morphology were unchanged. Finally, analysis of STED image stacks using Imaris software revealed that nuclear volume increased markedly prior to the onset of hypersegmentation and that nuclear size was differentially modulated by nocodazole and taxol in the presence and absence of infection. Taken together, our data define a new mechanism of hypersegmentation that is mediated by microtubules and dynein and as such advance understanding of processes that regulate nuclear morphology. |
topic |
neutrophils plasticity hypersegmentation microtubules dynein lamin B receptor |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.653100/full |
work_keys_str_mv |
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