Coxiella burnetii Virulent Phase I and Avirulent Phase II Variants Differentially Manipulate Autophagy Pathway in Neutrophils

dc.contributor.authorKumaresan, Venkatesh
dc.contributor.authorWang, Juexin
dc.contributor.authorZhang, Wendy
dc.contributor.authorZhang, Yan
dc.contributor.authorXu, Dong
dc.contributor.authorZhang, Guoquan
dc.contributor.departmentMedical and Molecular Genetics, School of Medicine
dc.date.accessioned2024-11-21T14:45:05Z
dc.date.available2024-11-21T14:45:05Z
dc.date.issued2022
dc.description.abstractCoxiella burnetii is an obligate intracellular Gram-negative bacterium that causes Q fever in humans. The virulent C. burnetii Nine Mile phase I (NMI) strain causes disease in animal models, while the avirulent NM phase II (NMII) strain does not. In this study, we found that NMI infection induces severe splenomegaly and bacterial burden in the spleen in BALB/c mice, while NMII infection does not. A significantly higher number of CD11b+ Ly6G+ neutrophils accumulated in the liver, lung, and spleen of NMI-infected mice than in NMII-infected mice. Thus, neutrophil accumulation correlates with NMI and NMII infection-induced inflammatory responses. In vitro studies also demonstrated that although NMII exhibited a higher infection rate than NMI in mouse bone marrow neutrophils (BMNs), NMI-infected BMNs survived longer than NMII-infected BMNs. These results suggest that the differential interactions of NMI and NMII with neutrophils may be related to their ability to cause disease in animals. To understand the molecular mechanism underlying the differential interactions of NMI and NMII with neutrophils, global transcriptomic gene expressions were compared between NMI- and NMII-infected BMNs by RNA sequencing (RNA-seq) analysis. Interestingly, several genes involved in autophagy-related pathways, particularly membrane trafficking and lipid metabolism, are upregulated in NMII-infected BMNs but downregulated in NMI-infected BMNs. Immunofluorescence and immunoblot analyses indicate that compared to NMI-infected BMNs, vacuoles in NMII-infected-BMNs exhibit increased autophagic flux along with phosphatidylserine translocation in the cell membrane. Similar to neutrophils, NMII activated LC3-mediated autophagy in human macrophages. These findings suggest that the differential manipulation of autophagy of NMI and NMII may relate to their pathogenesis.
dc.eprint.versionFinal published version
dc.identifier.citationKumaresan V, Wang J, Zhang W, Zhang Y, Xu D, Zhang G. Coxiella burnetii Virulent Phase I and Avirulent Phase II Variants Differentially Manipulate Autophagy Pathway in Neutrophils. Infect Immun. 2022;90(3):e0053421. doi:10.1128/IAI.00534-21
dc.identifier.urihttps://hdl.handle.net/1805/44655
dc.language.isoen_US
dc.publisherAmerican Society for Microbiology
dc.relation.isversionof10.1128/IAI.00534-21
dc.relation.journalInfection and Immunity
dc.rightsPublisher Policy
dc.sourcePMC
dc.subjectCoxiella burnetii
dc.subjectAutophagosome
dc.subjectDifferential gene expression
dc.subjectGlutathione
dc.subjectMembrane trafficking
dc.subjectNeutrophils
dc.subjectPathogenesis
dc.subjectPhosphatidylinositol
dc.subjectPI3 kinase
dc.subjectRNA-seq
dc.subjectAutophagy
dc.titleCoxiella burnetii Virulent Phase I and Avirulent Phase II Variants Differentially Manipulate Autophagy Pathway in Neutrophils
dc.typeArticle
ul.alternative.fulltexthttps://pmc.ncbi.nlm.nih.gov/articles/PMC8929353/
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