Involvement of Pore Formation and Osmotic Lysis in the Rapid Killing of Gamma Interferon-Pretreated C166 Endothelial Cells by Rickettsia prowazekii

Tropical Medicine and Infectious Disease, Journal Year: 2022, Volume and Issue: 7(8), P. 163 - 163

Published: Aug. 1, 2022

Rickettsia prowazekii, the bacterial cause of epidemic typhus in humans, proliferates mainly within microvascular endothelial cells. Previous studies have shown that murine macrophage-like RAW264.7 cells are rapidly damaged if they pretreated with gamma interferon (IFN-γ) and then infected R. prowazekii. In present study, effects IFN-γ prowazekii on C166 were evaluated. IFN-γ-pretreated prowazekii-infected cell cultures, evidence damage was observed several hours after addition rickettsiae. Considerable numbers became permeable to trypan blue dye ethidium bromide, substantial amounts lactate dehydrogenase (LDH) released from Such cellular injury not untreated cultures or any mock-infected cultures. Polyethylene glycols (PEGs) different nominal average molecular weights used assess possible involvement pore formation osmotic lysis this injury. PEG 8000 dramatically suppressed LDH release, 4000 partially inhibited it, PEGs 2000 1450 had no effect. Despite its inhibition did prevent staining by bromide. These findings suggest involves pores membranes, followed

Language: Английский

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Anaplasma phagocytophilum Transmission Activates Immune Pathways While Repressing Wound Healing in the Skin

Life, Journal Year: 2022, Volume and Issue: 12(12), P. 1965 - 1965

Published: Nov. 24, 2022

Anaplasma phagocytophilum, the causative agent of human granulocytic anaplasmosis (HGA), is an obligate intracellular bacterium transmitted by bite black-legged ticks, Ixodes scapularis. The main host cells in vertebrates are neutrophils. However, first site entry skin during tick feeding. Given that initial responses within a crucial determinant disease outcome vector-borne diseases, we used non-biased approach to characterize transcriptional changes take place at I. scapularis feeding and A. phagocytophilum transmission. Experimentally infected ticks were allowed feed for 3 days on C57BL/6J mice allow bacterial transmission establishment. Skin biopsies taken from attachment uninfected phagocytophilum-infected ticks. without (intact skin) was as baseline. RNA isolated sequenced using next-generation sequencing (NGS). differentially expressed genes identify over-represented pathways gene ontology (GO) pathway enrichment (PE). resulted activation interferon signaling neutrophil chemotaxis skin. Interestingly, it also led downregulation encoding extracellular matrix (ECM) components, upregulation metalloproteinases, suggesting delays wound healing may increase vascular permeability site.

Language: Английский

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Identification of common sequence motifs shared exclusively among selectively packed exosomal pathogenic microRNAs during rickettsial infections

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 7, 2023

We previously reported that microRNA (miR)23a and miR30b are selectively sorted into rickettsia-infected, endothelial cell-derived exosomes ( R -ECExos). Yet, the mechanism remains unknown. The number of cases spotted fever rickettsioses has been increasing in recent years, infections with these bacteria cause life-threatening diseases by targeting brain lung tissues. Therefore, aim present study is to continue dissect molecular underlying -ECExos-induced barrier dysfunction normal recipient microvascular cells (MECs), depending on their exosomal RNA cargos. Rickettsiae transmitted human hosts bite an infected tick skin. In we demonstrate treatment -ECExos, which were derived from group parkeri dermal MECs, induced disruptions paracellular adherens junctional protein VE-cadherin breached function pulmonary MECs (PMECs) RNA-dependent manner. Similarly, did not detect different levels miRs parent following rickettsial infections. However, demonstrated microvasculopathy-relevant miR23a-27a-24 cluster enriched -ECExos. Bioinformatic analysis revealed common sequence motifs shared exclusively among exosomal, selectively-enriched miR23a at levels. Taken together, data warrant further functional identification characterization a single, bipartition, or tripartition ACA, UCA, CAG guide recognition miR30b, subsequently results selective enrichments

Language: Английский

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