PMID- 36211967
OWN - NLM
STAT- MEDLINE
DCOM- 20221011
LR  - 20221013
IS  - 2235-2988 (Electronic)
IS  - 2235-2988 (Linking)
VI  - 12
DP  - 2022
TI  - Leishmania infection-induced multinucleated giant cell formation via upregulation 
      of ATP6V0D2 expression.
PG  - 953785
LID - 10.3389/fcimb.2022.953785 [doi]
LID - 953785
AB  - Leishmaniasis is caused by infection with protozoan parasites of the genus 
      Leishmania. In both clinical and experimental visceral leishmaniasis, macrophage 
      multinucleation is observed in parasitized tissues. However, the feature and the 
      mechanism of macrophage multinucleation remained unclear. Here, we report that 
      infection of Leishmania donovani, a causative agent of visceral leishmaniasis, 
      induces multinucleation of bone marrow-derived macrophages (BMDMs) in vitro. When 
      these infection-induced multinucleated macrophages were compared with 
      cytokine-induced multinucleated giant cells, the former had higher phagocytic 
      activity on red blood cells but no apparent changes on phagocytosis of latex 
      beads. BMDMs infected with L. donovani had increased expression of ATP6V0D2, one 
      of the components of V-ATPase, which was also upregulated in the spleen of 
      infected mice. Infection-induced ATP6V0D2 localized in a cytoplasmic compartment, 
      which did not overlap with the mitochondria, endoplasmic reticulum, or lysosomes. 
      When ATP6V0D2 expression was recombinantly induced in BMDMs, the formation of 
      multinucleated macrophages was induced as seen in the infected macrophages. Taken 
      together, L. donovani infection induces multinucleation of macrophages via 
      ATP6V0D2 upregulation leading to a unique metamorphosis of the macrophages toward 
      hemophagocytes.
CI  - Copyright (c) 2022 Hong, Sanjoba, Fujii, Yamagishi and Goto.
FAU - Hong, Jing
AU  - Hong J
AD  - Laboratory of Molecular Immunology, Graduate School of Agricultural and Life 
      Sciences, The University of Tokyo, Tokyo, Japan.
FAU - Sanjoba, Chizu
AU  - Sanjoba C
AD  - Laboratory of Molecular Immunology, Graduate School of Agricultural and Life 
      Sciences, The University of Tokyo, Tokyo, Japan.
FAU - Fujii, Wataru
AU  - Fujii W
AD  - Laboratory of Applied Genetics, Graduate School of Agricultural and Life 
      Sciences, The University of Tokyo, Tokyo, Japan.
FAU - Yamagishi, Junya
AU  - Yamagishi J
AD  - International Collaboration Unit, International Institute for Zoonosis Control, 
      Hokkaido University, Sapporo, Japan.
FAU - Goto, Yasuyuki
AU  - Goto Y
AD  - Laboratory of Molecular Immunology, Graduate School of Agricultural and Life 
      Sciences, The University of Tokyo, Tokyo, Japan.
LA  - eng
PT  - Journal Article
DEP - 20220923
PL  - Switzerland
TA  - Front Cell Infect Microbiol
JT  - Frontiers in cellular and infection microbiology
JID - 101585359
RN  - 0 (Cytokines)
RN  - EC 3.6.1.- (Adenosine Triphosphatases)
RN  - EC 3.6.1.- (Atp6v0d2 protein, mouse)
RN  - EC 3.6.1.- (Vacuolar Proton-Translocating ATPases)
SB  - IM
MH  - Adenosine Triphosphatases
MH  - Animals
MH  - Cytokines
MH  - Giant Cells
MH  - *Leishmania donovani
MH  - *Leishmaniasis, Visceral/parasitology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Up-Regulation
MH  - *Vacuolar Proton-Translocating ATPases
PMC - PMC9539756
OTO - NOTNLM
OT  - ATP6V0D2
OT  - Leishmania
OT  - hemophagocytosis
OT  - macrophage
OT  - multinucleated giant cell (MGC)
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/10/11 06:00
MHDA- 2022/10/12 06:00
PMCR- 2022/01/01
CRDT- 2022/10/10 04:03
PHST- 2022/05/26 00:00 [received]
PHST- 2022/08/29 00:00 [accepted]
PHST- 2022/10/10 04:03 [entrez]
PHST- 2022/10/11 06:00 [pubmed]
PHST- 2022/10/12 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fcimb.2022.953785 [doi]
PST - epublish
SO  - Front Cell Infect Microbiol. 2022 Sep 23;12:953785. doi: 
      10.3389/fcimb.2022.953785. eCollection 2022.