PMID- 25024369
OWN - NLM
STAT- MEDLINE
DCOM- 20141112
LR  - 20211021
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 82
IP  - 10
DP  - 2014 Oct
TI  - Type II Toxoplasma gondii induction of CD40 on infected macrophages enhances 
      interleukin-12 responses.
PG  - 4047-55
LID - 10.1128/IAI.01615-14 [doi]
AB  - Toxoplasma gondii is an obligate intracellular parasite that can cause severe 
      neurological disease in infected humans. CD40 is a receptor on macrophages that 
      plays a critical role in controlling T. gondii infection. We examined the 
      regulation of CD40 on the surface of T. gondii-infected bone marrow-derived 
      macrophages (BMdMs). T. gondii induced CD40 expression both at the transcript 
      level and on the cell surface, and interestingly, the effect was parasite strain 
      specific: CD40 levels were dramatically increased in type II T. gondii-infected 
      BMdMs compared to type I- or type III-infected cells. Type II induction of CD40 
      was specific to cells harboring intracellular parasites and detectable as early 
      as 6 h postinfection (hpi) at the transcript level. CD40 protein expression 
      peaked at 18 hpi. Using forward genetics with progeny from a type II x type III 
      cross, we found that CD40 induction mapped to a region of chromosome X that 
      included the gene encoding the dense granule protein 15 (GRA15). Using type I 
      parasites stably expressing the type II allele of GRA15 (GRA15II), we found that 
      type I GRA15II parasites induced the expression of CD40 on infected cells in an 
      NF-kappaB-dependent manner. In addition, stable expression of hemagglutinin-tagged 
      GRA15II in THP-1 cells resulted in CD40 upregulation in the absence of infection. 
      Since CD40 signaling contributes to interleukin-12 (IL-12) production, we 
      examined IL-12 from infected macrophages and found that CD40L engagement of CD40 
      amplified the IL-12 response in type II-infected cells. These data indicate that 
      GRA15II induction of CD40 promotes parasite immunity through the production of 
      IL-12.
CI  - Copyright (c) 2014, American Society for Microbiology. All Rights Reserved.
FAU - Morgado, Pedro
AU  - Morgado P
AD  - Department of Molecular Biology and Biochemistry, University of California, 
      Irvine, Irvine, California, USA Institute for Immunology, University of 
      California, Irvine, Irvine, California, USA.
FAU - Sudarshana, Dattanand M
AU  - Sudarshana DM
AD  - Department of Molecular Biology and Biochemistry, University of California, 
      Irvine, Irvine, California, USA Institute for Immunology, University of 
      California, Irvine, Irvine, California, USA.
FAU - Gov, Lanny
AU  - Gov L
AD  - Department of Molecular Biology and Biochemistry, University of California, 
      Irvine, Irvine, California, USA Institute for Immunology, University of 
      California, Irvine, Irvine, California, USA.
FAU - Harker, Katherine S
AU  - Harker KS
AD  - Department of Molecular Biology and Biochemistry, University of California, 
      Irvine, Irvine, California, USA Institute for Immunology, University of 
      California, Irvine, Irvine, California, USA.
FAU - Lam, Tonika
AU  - Lam T
AD  - Department of Molecular Biology and Biochemistry, University of California, 
      Irvine, Irvine, California, USA Institute for Immunology, University of 
      California, Irvine, Irvine, California, USA Department of Microbiology and 
      Molecular Genetics, University of California, Irvine, Irvine, California, USA.
FAU - Casali, Paolo
AU  - Casali P
AD  - Department of Molecular Biology and Biochemistry, University of California, 
      Irvine, Irvine, California, USA Institute for Immunology, University of 
      California, Irvine, Irvine, California, USA Department of Microbiology and 
      Molecular Genetics, University of California, Irvine, Irvine, California, USA.
FAU - Boyle, Jon P
AU  - Boyle JP
AD  - Department of Biological Sciences, Dietrich School of Arts and Sciences, 
      University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
FAU - Lodoen, Melissa B
AU  - Lodoen MB
AD  - Department of Molecular Biology and Biochemistry, University of California, 
      Irvine, Irvine, California, USA Institute for Immunology, University of 
      California, Irvine, Irvine, California, USA mlodoen@uci.edu.
LA  - eng
GR  - T32 AI060573/AI/NIAID NIH HHS/United States
GR  - R25GM055246/GM/NIGMS NIH HHS/United States
GR  - R01 AI105813/AI/NIAID NIH HHS/United States
GR  - T32AI60573/AI/NIAID NIH HHS/United States
GR  - R25 GM055246/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140714
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Antigens, Protozoan)
RN  - 0 (CD40 Antigens)
RN  - 0 (Protozoan Proteins)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Animals
MH  - Antigens, Protozoan/immunology
MH  - CD40 Antigens/*biosynthesis/*immunology
MH  - Cells, Cultured
MH  - Humans
MH  - Interleukin-12/*immunology
MH  - Macrophages/*immunology/*parasitology
MH  - Protozoan Proteins/*immunology
MH  - Toxoplasma/*immunology
PMC - PMC4187859
EDAT- 2014/07/16 06:00
MHDA- 2014/11/13 06:00
PMCR- 2015/04/01
CRDT- 2014/07/16 06:00
PHST- 2014/07/16 06:00 [entrez]
PHST- 2014/07/16 06:00 [pubmed]
PHST- 2014/11/13 06:00 [medline]
PHST- 2015/04/01 00:00 [pmc-release]
AID - IAI.01615-14 [pii]
AID - 01615-14 [pii]
AID - 10.1128/IAI.01615-14 [doi]
PST - ppublish
SO  - Infect Immun. 2014 Oct;82(10):4047-55. doi: 10.1128/IAI.01615-14. Epub 2014 Jul 
      14.