Infection-generated electric field in gut epithelium drives bidirectional migration of macrophages

Sun, Yaohui; Reid, Brian; Ferreira, Fernando; Luxardi, Guillaume; Ma, Li; Lokken, Kristen L.; Zhu, Kan; Xu, Gege; Sun, Yuxin; Ryzhuk, Volodymyr; Guo, Betty P.; Lebrilla, Carlito B.; Maverakis, Emanual; Mogilner, Alex; Zhao, Min

doi:10.1101/427294

Cited by 8 publications

(9 citation statements)

References 96 publications

(97 reference statements)

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“…In the field of macrophages, human monocyte-derived macrophages (dcEF: 5–300 mV/mm, 2 h) [ 9 ], mouse bone marrow-derived macrophages (dcEF: 300 mV/mm, 4 h) [ 11 ], mouse peritoneal macrophages (PMs) and bone marrow-derived macrophages (BMDMs) (dcEF: 400 mV/mm, 3 h) [ 12 ] have been used to study various biological effects of electric fields on macrophages. The interpretation of the above results suggests that the proper stimulation condition of an electric field on cells is in the range of 100–400 mV/mm (0.5–8 h).…”

Section: Discussionmentioning

confidence: 99%

“…Very recently, Yaohui Sun et al showed that a Salmonella infection generates an electric field in the gut epithelium of the mouse cecum, which drives the bidirectional migration of macrophages. By using primary mouse peritoneal macrophages (PMs) and bone marrow-derived macrophages (BMDMs), they mimic the infection-generated electric field by exposing macrophages with electric field (dcEF: 400 mV/mm, 3 h), and they also found that Salmonella infection switches macrophage galvanotaxis from the anode to the cathode [ 12 ]. Taken together, the above studies suggest that the electric field is a new regulatory element that determines the function of macrophages.…”

Section: Introductionmentioning

confidence: 99%

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Hub Proteins Involved in RAW 264.7 Macrophages Exposed to Direct Current Electric Field

Liu

et al. 2020

IJMS

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At present, studies on macrophage proteins mainly focus on biological stimuli, with less attention paid to the responses of macrophage proteins to physical stimuli, such as electric fields. Here, we exploited the electric field-sensitive hub proteins of macrophages. RAW 264.7 macrophages were treated with a direct current electric field (dcEF) (200 mV/mm) for four hours, followed by RNA-Seq analysis. Differentially expressed genes (DEGs) were obtained, followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) and protein–protein interaction (PPI) analysis. Eight qPCR-verified DEGs were selected. Subsequently, three-dimensional protein models of DEGs were modeled by Modeller and Rosetta, followed by molecular dynamics simulation for 200 ns with GROMACS. Finally, dcEFs (10, 50, and 500 mV/mm) were used to simulate the molecular dynamics of DEG proteins for 200 ns, followed by trajectory analysis. The dcEF has no obvious effect on RAW 264.7 morphology. A total of 689 DEGs were obtained, and enrichment analysis showed that the steroid biosynthesis pathway was most affected by the dcEF. Moreover, the three-dimensional protein structures of hub proteins were constructed, and trajectory analysis suggested that the dcEF caused an increase in the atomic motion of the protein in a dcEF-intensity-dependent manner. Overall, we provide new clues and a basis for investigating the hub proteins of macrophages in response to electric field stimulation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hub Proteins Involved in RAW 264.7 Macrophages Exposed to Direct Current Electric Field

Liu

et al. 2020

IJMS

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“…To explore this possibility and to gain insights into the mechanism of electrotaxis in vivo, we investigated how neural crest cells sense and transduce endogenous electric fields into a directional cue. Most of the proteins reported to mediate electrotaxis are part of the cell selfpolarity 20,21 or cell-substrate adhesion 22,23 machineries and few molecules have been shown to specifically mediate electrotaxis in vitro [24][25][26][27] . Hence, the precise mechanism used by cells to transduce electric fields into a directional response in vivo remains unclear.…”

Section: Mainmentioning

confidence: 99%

Stretch-induced endogenous electric fields drive neural crest directed collective cell migration in vivo

Ferreira

Moreira

Barriga

2021

Preprint

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Directed collective cell migration (dCCM) is essential for morphogenesis. Cell clusters migrate in inherently complex in vivo environments composed of chemical, electrical, mechanical as well as topological features. While these environmental factors have been shown to allow dCCM in vitro, our understanding of dCCM in vivo is mostly limited to chemical guidance. Thus, despite its wide biological relevance, the mechanisms that guide dCCM in vivo remain unclear. To address this, we study endogenous electric fields in relation to the migratory environment of the Xenopus laevis cephalic neural crest, an embryonic cell population that collectively and directionally migrates in vivo. Combining bioelectrical, biomechanical and molecular tools, we show that endogenous electric fields drive neural crest dCCM via electrotaxis in vivo. Moreover, we identify the voltage-sensitive phosphatase 1 (Vsp1) as a key component of the molecular mechanism used by neural crest cells to transduce electric fields into a directional cue. Furthermore, Vsp1 function is specifically required for electrotaxis, being dispensable for cell motility and chemotaxis. Finally, we reveal that endogenous electric fields are mechanoelectrically established. Mechanistically, convergent extension movements of the neural fold generate membrane tension, which in turn opens stretch-activated channels to mobilise the ions required to fuel electric fields. Overall, our results reveal a mechanism of cell guidance, where electrotaxis emerges from the mechanoelectrical and molecular interplay between neighbouring tissues. More broadly, our data contribute to validate the, otherwise understudied, functions of endogenous bioelectrical stimuli in morphogenetic processes.

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“…Salmonella initially colonizes the small intestine and invades IECs, overcoming the mucosal barrier and manipulating the immune response through translocation of various effector molecules [28][29][30] . It can bypass humoral immunity by hijacking phagocytes to egress from the gut into the lymphatic system or bloodstream, potentially causing life-threatening systemic infections 31 . The above-described influence of HIF-1 on cellular immune functions as well as tight sealing of the intestinal wall therefore led us to investigate its role during gastrointestinal infections, using Salmonella enterica subsp.…”

Section: Introductionmentioning

confidence: 99%

Conditional deletion of HIF-1α provides new insight regarding the murine response to gastrointestinal infection withSalmonellaTyphimurium

Robrahn

Dupont

Jumpertz

et al. 2021

Preprint

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The hypoxia-inducible transcription factor 1 (HIF-1) has been shown to ameliorate different bacterial infections through enhancement of microbial killing. While the impact of HIF-1 on inflammatory diseases of the gut has been studied intensively, its function in bacterial infections of the intestine remains largely elusive. With the help of a publicly available gene expression data set, we could infer significant activation of the HIF-1 transcription factor after oral infection of mice with Salmonella Typhimurium. This prompted us to apply lineage-restricted deletion of the Hif1a locus in mice to examine cell type-specific functions of HIF-1 in this model. We show hypoxia-independent induction of HIF-1 activity upon Salmonella infection in the intestinal epithelium as well as in macrophages. Surprisingly, Hif1a deletion in intestinal epithelial cells impacted neither disease outcome nor inflammatory activity. The conditional knockout of Hif1a in myeloid cells enhanced the mRNA expression of the largely pro-inflammatory chemokine Cxcl2, revealing a potentially inflammatory effect of HIF-1 deficiency in myeloid cells in the gut in vivo. Again, the disease outcome was not affected. In vitro HIF-1-deficient macrophages showed an overall impaired transcription of pro-inflammatory factors, however, Salmonella bypassed direct intracellular, bactericidal HIF-1-dependent mechanisms in a Salmonella pathogenicity island (SPI)-2 independent manner. Taken together, our data suggest that HIF-1 in intestinal epithelial and myeloid cells is either dispensable or compensable in the immune defense against Salmonella Typhimurium.

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Infection-generated electric field in gut epithelium drives bidirectional migration of macrophages

Cited by 8 publications

References 96 publications

Hub Proteins Involved in RAW 264.7 Macrophages Exposed to Direct Current Electric Field

Hub Proteins Involved in RAW 264.7 Macrophages Exposed to Direct Current Electric Field

Stretch-induced endogenous electric fields drive neural crest directed collective cell migration in vivo

Conditional deletion of HIF-1α provides new insight regarding the murine response to gastrointestinal infection withSalmonellaTyphimurium

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