PMID- 33013831
OWN - NLM
STAT- MEDLINE
DCOM- 20210419
LR  - 20210419
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 11
DP  - 2020
TI  - Attenuated P. falciparum Parasite Shows Cytokine Variations in Humanized Mice.
PG  - 1801
LID - 10.3389/fimmu.2020.01801 [doi]
LID - 1801
AB  - A recently developed humanized mouse has been used to assess the immune response 
      evoked against the isolated attenuated C9 parasite clone (C9-M; carrying a single 
      insertion disrupting the open reading frame (ORF) of PF3D7_1305500) of Plasmodium 
      falciparum. Significant human RBC engraftment was achieved by ameliorating the 
      residual non-adaptive immune response using clodronate-loaded liposome treatment. 
      Controlled reactive professional phagocytic leukocytes in immunodeficient mice 
      allowed for sizeable human blood chimerism and injected huRBCs acted as bona fide 
      host cells for P. falciparum. huRBC-reconstituted immunodeficient mice received 
      infectious challenge with attenuated P. falciparum C9 parasite mutants (C9-M), 
      complemented (C9-C), and wild type (NF54) progenitors to study the role of immune 
      effectors in the clearance of the parasite from mouse circulation. C9-M and NF54 
      parasites grew and developed in the huRBC-reconstituted humanized NSG mice. 
      Further, the presence of mutant parasites in deep-seated tissues suggests the 
      escape of parasites from the host's immune responses and thus extended the 
      survival of the parasite. Our results suggest an evasion mechanism that may have 
      been employed by the parasite to survive the mouse's residual non-adaptive immune 
      responses. Collectively, our data suggest that huRBCs reconstituted NSG mice 
      infected with attenuated P. falciparum is a valuable tool to explore the role of 
      C9 mutation in the growth and survival of parasite mutants and their response to 
      the host's immune responses. This mouse might help in identifying novel 
      chemotherapeutic targets to develop new anti-malarial drugs.
CI  - Copyright (c) 2020 Zhang, Li, Ji, Tian, Wang, Chen and Tian.
FAU - Zhang, Lei-Lei
AU  - Zhang LL
AD  - Department of Anesthesiology, The Second Hospital of Jilin University, Changchun, 
      China.
FAU - Li, Jin-Long
AU  - Li JL
AD  - Department of Gastrointestinal Surgery, The Second Hospital of Jilin University, 
      Changchun, China.
FAU - Ji, Ming-Xin
AU  - Ji MX
AD  - Department of Anesthesiology, The Second Hospital of Jilin University, Changchun, 
      China.
FAU - Tian, Dan
AU  - Tian D
AD  - Department of Anesthesiology, The Second Hospital of Jilin University, Changchun, 
      China.
FAU - Wang, Li-Yan
AU  - Wang LY
AD  - Department of Operating Room, The Second Hospital of Jilin University, Changchun, 
      China.
FAU - Chen, Chen
AU  - Chen C
AD  - Department of Operating Room, The Second Hospital of Jilin University, Changchun, 
      China.
FAU - Tian, Miao
AU  - Tian M
AD  - Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, 
      Changchun, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200911
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Cytokines)
RN  - 0 (Protozoan Proteins)
SB  - IM
MH  - Animals
MH  - Cytokines/*blood
MH  - Disease Models, Animal
MH  - Erythrocyte Transfusion
MH  - Erythrocytes/*immunology/metabolism/parasitology
MH  - Female
MH  - Host-Parasite Interactions
MH  - Humans
MH  - *Immune Evasion
MH  - *Immunity, Innate
MH  - Malaria, Falciparum/blood/*immunology/parasitology
MH  - Male
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Mutation
MH  - Parasite Load
MH  - Plasmodium falciparum/genetics/*immunology/pathogenicity
MH  - Protozoan Proteins/genetics
MH  - Time Factors
PMC - PMC7516016
OTO - NOTNLM
OT  - C9 parasite mutants (C9-M)
OT  - NOD/SCID/IL-2rg-/ (NSG) growth mutants
OT  - PF3D7_1305500
OT  - TK/NOG
OT  - clodronate-loaded liposomes
OT  - complemented parasites (C9-C)
OT  - cytokine
OT  - humanized mice
EDAT- 2020/10/06 06:00
MHDA- 2021/04/20 06:00
PMCR- 2020/01/01
CRDT- 2020/10/05 06:16
PHST- 2020/04/24 00:00 [received]
PHST- 2020/07/06 00:00 [accepted]
PHST- 2020/10/05 06:16 [entrez]
PHST- 2020/10/06 06:00 [pubmed]
PHST- 2021/04/20 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2020.01801 [doi]
PST - epublish
SO  - Front Immunol. 2020 Sep 11;11:1801. doi: 10.3389/fimmu.2020.01801. eCollection 
      2020.