PMID- 11698470
OWN - NLM
STAT- MEDLINE
DCOM- 20011207
LR  - 20190515
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 167
IP  - 10
DP  - 2001 Nov 15
TI  - Plasmodium berghei infection in mice induces liver injury by an IL-12- and 
      toll-like receptor/myeloid differentiation factor 88-dependent mechanism.
PG  - 5928-34
AB  - Malaria, caused by infection with Plasmodium spp., is a life cycle-specific 
      disease that includes liver injury at the erythrocyte stage of the parasite. In 
      this study, we have investigated the mechanisms underlying Plasmodium 
      berghei-induced liver injury, which is characterized by the presence of apoptotic 
      and necrotic hepatocytes and dense infiltration of lymphocytes. Although both 
      IL-12 and IL-18 serum levels were elevated after infection, IL-12-deficient, but 
      not IL-18-deficient, mice were resistant to liver injury induced by P. berghei. 
      Neither elevation of serum IL-12 levels nor liver injury was observed in mice 
      deficient in myeloid differentiation factor 88 (MyD88), an adaptor molecule 
      shared by Toll-like receptors (TLRs). These results demonstrated a requirement of 
      the TLR-MyD88 pathway for induction of IL-12 production during P. berghei 
      infection. Hepatic lymphocytes from P. berghei-infected wild-type mice lysed 
      hepatocytes from both uninfected and infected mice. The hepatocytotoxic action of 
      these cells was blocked by a perforin inhibitor but not by a neutralizing 
      anti-Fas ligand Ab and was up-regulated by IL-12. Surprisingly, these cells 
      killed hepatocytes in an MHC-unrestricted manner. However, CD1d-deficient mice 
      that lack CD1d-restricted NK T cells, were susceptible to liver injury induced by 
      P. berghei. Collectively, our results indicate that the liver injury induced by 
      P. berghei infection of mice induces activation of the TLR-MyD88 signaling 
      pathway which results in IL-12 production and activation of the 
      perforin-dependent cytotoxic activities of MHC-unrestricted hepatic lymphocytes.
FAU - Adachi, K
AU  - Adachi K
AD  - Department of Immunology and Medical Zoology, Institute for Advanced Medical 
      Science, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
FAU - Tsutsui, H
AU  - Tsutsui H
FAU - Kashiwamura, S
AU  - Kashiwamura S
FAU - Seki, E
AU  - Seki E
FAU - Nakano, H
AU  - Nakano H
FAU - Takeuchi, O
AU  - Takeuchi O
FAU - Takeda, K
AU  - Takeda K
FAU - Okumura, K
AU  - Okumura K
FAU - Van Kaer, L
AU  - Van Kaer L
FAU - Okamura, H
AU  - Okamura H
FAU - Akira, S
AU  - Akira S
FAU - Nakanishi, K
AU  - Nakanishi K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antigens, CD1)
RN  - 0 (Antigens, CD1d)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Fasl protein, mouse)
RN  - 0 (Interleukin-18)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Pore Forming Cytotoxic Proteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (fas Receptor)
RN  - 126465-35-8 (Perforin)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Antigens, CD1/analysis
MH  - Antigens, CD1d
MH  - Antigens, Differentiation/genetics/*physiology
MH  - Cytotoxicity Tests, Immunologic
MH  - *Drosophila Proteins
MH  - Fas Ligand Protein
MH  - Female
MH  - Hepatitis, Animal/etiology/*parasitology/pathology
MH  - Interleukin-12/genetics/*physiology
MH  - Interleukin-18/genetics/physiology
MH  - Killer Cells, Natural/immunology
MH  - Liver/pathology
MH  - Malaria/*etiology/pathology
MH  - Membrane Glycoproteins/genetics/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Myeloid Differentiation Factor 88
MH  - Perforin
MH  - *Plasmodium berghei
MH  - Pore Forming Cytotoxic Proteins
MH  - Receptors, Cell Surface/*physiology
MH  - *Receptors, Immunologic
MH  - T-Lymphocyte Subsets/immunology
MH  - Toll-Like Receptors
MH  - fas Receptor/physiology
EDAT- 2001/11/08 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/11/08 10:00
PHST- 2001/11/08 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/11/08 10:00 [entrez]
AID - 10.4049/jimmunol.167.10.5928 [doi]
PST - ppublish
SO  - J Immunol. 2001 Nov 15;167(10):5928-34. doi: 10.4049/jimmunol.167.10.5928.