PMID- 35100012
OWN - NLM
STAT- MEDLINE
DCOM- 20220420
LR  - 20220918
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 90
IP  - 3
DP  - 2022 Mar 17
TI  - Coxiella burnetii Virulent Phase I and Avirulent Phase II Variants Differentially 
      Manipulate Autophagy Pathway in Neutrophils.
PG  - e0053421
LID - 10.1128/IAI.00534-21 [doi]
LID - e00534-21
AB  - Coxiella 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.
FAU - Kumaresan, Venkatesh
AU  - Kumaresan V
AUID- ORCID: 0000-0003-1950-6231
AD  - Department of Molecular Microbiology and Immunology, University of Texas at San 
      Antonio, San Antonio, Texas, USA.
AD  - Department of Veterinary Pathobiology, University of 
      Missourigrid.134936.agrid.418801.4-Columbia, Columbia, Missouri, USA.
FAU - Wang, Juexin
AU  - Wang J
AD  - Department of Electrical Engineering and Computer Science, University of 
      Missourigrid.134936.agrid.418801.4-Columbia, Columbia, Missouri, USA.
FAU - Zhang, Wendy
AU  - Zhang W
AD  - Department of Molecular Microbiology and Immunology, University of Texas at San 
      Antonio, San Antonio, Texas, USA.
FAU - Zhang, Yan
AU  - Zhang Y
AD  - Department of Molecular Microbiology and Immunology, University of Texas at San 
      Antonio, San Antonio, Texas, USA.
AD  - Department of Veterinary Pathobiology, University of 
      Missourigrid.134936.agrid.418801.4-Columbia, Columbia, Missouri, USA.
FAU - Xu, Dong
AU  - Xu D
AD  - Department of Electrical Engineering and Computer Science, University of 
      Missourigrid.134936.agrid.418801.4-Columbia, Columbia, Missouri, USA.
FAU - Zhang, Guoquan
AU  - Zhang G
AUID- ORCID: 0000-0002-7273-8755
AD  - Department of Molecular Microbiology and Immunology, University of Texas at San 
      Antonio, San Antonio, Texas, USA.
AD  - Department of Veterinary Pathobiology, University of 
      Missourigrid.134936.agrid.418801.4-Columbia, Columbia, Missouri, USA.
LA  - eng
GR  - R21AI149044/HHS | NIH | National Institute of Allergy and Infectious Diseases 
      (NIAID)/
GR  - R21AI141945/HHS | NIH | National Institute of Allergy and Infectious Diseases 
      (NIAID)/
GR  - R21 AI149044/AI/NIAID NIH HHS/United States
GR  - R01 AI134681/AI/NIAID NIH HHS/United States
GR  - R01AI134681/HHS | NIH | National Institute of Allergy and Infectious Diseases 
      (NIAID)/
GR  - R21 AI141945/AI/NIAID NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20220131
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
SB  - IM
MH  - Animals
MH  - Autophagy
MH  - *Coxiella burnetii
MH  - Macrophages/microbiology
MH  - Mice
MH  - Neutrophils/metabolism
MH  - *Q Fever/microbiology
PMC - PMC8929353
OTO - NOTNLM
OT  - Coxiella burnetii
OT  - PI3 kinase
OT  - RNA-seq
OT  - autophagosome
OT  - autophagy
OT  - differential gene expression
OT  - glutathione
OT  - membrane trafficking
OT  - neutrophils
OT  - pathogenesis
OT  - phosphatidylinositol
COIS- The authors declare no conflict of interest.
EDAT- 2022/02/01 06:00
MHDA- 2022/04/21 06:00
PMCR- 2022/09/17
CRDT- 2022/01/31 17:13
PHST- 2022/02/01 06:00 [pubmed]
PHST- 2022/04/21 06:00 [medline]
PHST- 2022/01/31 17:13 [entrez]
PHST- 2022/09/17 00:00 [pmc-release]
AID - 00534-21 [pii]
AID - iai.00534-21 [pii]
AID - 10.1128/IAI.00534-21 [doi]
PST - ppublish
SO  - Infect Immun. 2022 Mar 17;90(3):e0053421. doi: 10.1128/IAI.00534-21. Epub 2022 
      Jan 31.