Mouse treatment


The effects of experimental treatments and genetic interventions (gene knockout) on the course of infection and pathology in murine malaria models are listed in this part of the database. For each molecule, data about the genetic background of the mouse strain (and number of backcrosses), parasite species, inoculum size (pRBC), details of the treatment/knockout, effect on parasitemia, pathology and survival, additional data of the effects of the treatments (e.g. on expression of other factors), references (Refs), and a hyperlink to the original paper in the PubMed database (U.S. National Library of Medicine, National Institutes of Health) is included.

Dynamic fields: these are the columns that you can select to show in the output table. See also "How to use MalarImDB?" for more information.

Abbreviations: ALI, acute lung injury; anti-…; treatment with depleting antibodies; CM, experimental cerebral malaria (when indicated the incidence is included between brackets, e.g. CM (100%) means that 100% of the mice suffered from cerebral pathology); EG, experimental group; HP&A, hyperparasitemia and anemia; i.p., intraperitoneal administration; MA-ARDS, malaria-associated acute respiratory distress syndrome; N.I., not indicated; p.o., oral administration; r, recombinant; R, receptor; s, soluble; male mice; female mice; -/-, gene knockout mice; +, and/positive (example1: rIL-1a + anti-IFN-g: mice were treated with recombinant IL-1a and antibodies to deplete IFN-g; example2: CD4+ T cells, CD4 positive T cells); ↑, increased; ↓, decreased; ~, on average

 

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Molecular group
Molecule/Cell
Plasmodium strain
pRBC infection titer
Mouse genetic background (Con)
Level of backcrossing
Experimental treatment group (EG)
Lethal infection (Con)
Lethal infection (EG)
Pathology (Con)
Pathology (EG)
Parasitemia (EG vs Con)
Additional phenotypes (EG vs Con)
Refs
PubMed
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Full Molecule/Cell Plasmodium strain Mouse genetic background (Con) Experimental treatment group (EG) Lethal infection (Con) Lethal infection (EG) Pathology (Con) Pathology (EG) Parasitemia (EG vs Con) Additional phenotypes (EG vs Con) Refs PubMed
EPO Plasmodium chabaudi AS A/J rmEpo yes (100%) yes (50%) SMA (100%) SMA (50%) Similar Increased reticulocytosis; similar anemia; survived a challenge infection 5 weeks after primary infection Chang et al., 2004, J Infect Dis
EPO Plasmodium chabaudi AS C57BL/6 rmEpo no yes (% depended on the time of administration) N.I. SMA (% depended on the time of administration) Increased and delayed clearance Earlier increase in reticulocytosis Chang et al., 2004, J Infect Dis
Fas Plasmodium berghei ANKA C57BL/6 Fas -/- (lpr) yes yes CM (100%) CM (100%) N.I. N.I. Nitcheu et al., 2003, J Immunol
Fas Plasmodium berghei ANKA C57BL/6 Fas -/- (lpr) yes yes CM CM (50%) Similar Heterozygotes not different from WT Ohno et al., 2005, Immunogenetics
Fas Plasmodium berghei ANKA CBA/N Fas -/- (lpr) yes yes CM CM (50%) Similar Heterozygotes not different from WT Ohno et al., 2005, Immunogenetics
Fas Plasmodium berghei ANKA C57BL/6 for WT, N.I. for Lpr Fas -/- (lpr) yes yes CM resolving CM and died from HP&A Similar Mice displayed all the cerebral symptoms of CM around day 6-8 (hemorrhages, edema, leukocyte sequestration), but recovered from all the symptoms and died later of overwhelming parasitemia; similar splenomegaly; deposits of hemozoin in the brain parenchyma presumably from previous hemorrhages or pRBC sequestration; similar CD8 and CD4 mRNA expression in spleen and similar CD8, CD4, TNF-a, perforin and granzyme B mRNA expression in brain; no apoptotic astrocytes in retinal wholemount tissue (IHC) Potter et al., 2006, J Neuroimmunol
Fas Plasmodium berghei K173 C57BL/6 for WT, N.I. for Lpr Fas -/- (lpr) yes yes HP&A HP&A Similar Similar hematocrit and splenomegaly, no cerebral pathology (similar to WT mice) Potter et al., 2006, J Neuroimmunol
Fas Plasmodium berghei NK65 C57BL/6 Fas -/- (lpr) yes yes Liver pathology Liver pathology N.I. Similar serum GPT (ALT), liver injury and lymphocyte infiltration in liver Adachi et al., 2001, J Immunol
Fas Plasmodium yoelii 17XNL C57BL/6 Fas -/- (lpr) no no None None Increased peak and delayed clearance N.I. Ohno et al., 2005, Immunogenetics
Fas Plasmodium yoelii 17XNL C3H/HeJ Fas -/- (lpr) no no None None Similar N.I. Ohno et al., 2005, Immunogenetics
Fas Plasmodium yoelii 17XNL MRL/MpJ Fas -/- (lpr) no no None None Similar N.I. Ohno et al., 2005, Immunogenetics
FasL Plasmodium berghei ANKA C57BL/6 FasL -/- (gld) yes yes CM (100%) CM (100%) N.I. N.I. Nitcheu et al., 2003, J Immunol
FasL Plasmodium berghei ANKA C57BL/6 for WT, N.I. for Gld FasL -/- (gld) yes yes CM resolving CM and died from HP&A Similar Mice displayed all the cerebral symptoms of CM around day 6-8 (hemorrhages, edema, leukocyte sequestration), but recovered from all the symptoms and died later of overwhelming parasitemia; similar splenomegaly; deposits of hemozoin in the brain parenchyma presumably from previous hemorrhages or pRBC sequestration; similar CD8 and CD4 mRNA expression in spleen and similar CD8, CD4, TNF-a, perforin and granzyme B mRNA expression in brain; no apoptotic astrocytes in retinal wholemount tissue (IHC) Potter et al., 2006, J Neuroimmunol
FasL Plasmodium berghei K173 C57BL/6 for WT, N.I. for Gld FasL -/- (gld) yes yes HP&A HP&A Similar Similar hematocrit and splenomegaly, no cerebral pathology (similar to WT mice) Potter et al., 2006, J Neuroimmunol
FcgR Plasmodium berghei XAT C57BL/6 FcRg -/- no yes N.I. N.I. No parasite clearance ↓ phagocytic activity by splenic macrophages; similar IFN-g production by spleen cells; similar total IgG, IgG1, IgG2a, IgG2b and IgG3; passive transfer of anti-XAT IgG failed to suppress the increase in parasitemia Yoneto et al., 2001, J Immunol
FcgR Plasmodium yoelii 17XL BALB/cByJ FcRg -/- yes yes N.I. N.I. Similar Passive transfer of hyperimmune mice sera protected equally Rotman et al., 1998, J Immunol
FcgRI Plasmodium berghei tg for P. falciparum MSP19 Tg BALB/c x BALB/c F1 Hu-FcRI-tg + anti-PfMSP-1 yes no N.I. N.I. Decreased (undetectable) N.I. McIntosh et al., 2007, PLoS Pathog
FcgRIIB Plasmodium berghei ANKA C57BL/6 FcgRIIB-/- (SLE-susceptible) yes yes CM (60%) CM (10%) Similar Prolonged survival (~1 week); ↑ splenomegaly 7 days p.i.; no kidney inflammation Waisberg et al., 2010, Proc Natl Acad Sci U S A
FcgRIIB Plasmodium chabaudi chabaudi BALB/c FcgRIIB-/- (SLE-susceptible) no ni N.I. N.I. Decreased peak and more rapid clearance ↓ anemia and hypothermia; ↑ expression of CD86, production of TNF and phagocytosis of iRBCs by macrophages in vitro; ↑ antimalarial IgG Clatworthy et al., 2007, Proc Natl Acad Sci U S A
FcgRIIB/TLR7 Plasmodium berghei ANKA C57BL/6 FcgRIIB-/-.yaa (SLE-susceptible), contains a duplication of TLR7 yes yes CM (90%) CM (10%) Similar Prolonged survival (~1 week); ↑ splenomegaly 7 days p.i.; ↓ postmortem brain and similar kidney weight; developped moderated kidney inflammation; ↓ number of brain microhemorrhages; ↑ serum GM-CSF and IL-10 before infection; similar levels of serum GM-CSF and ↓ IL-10, IFN-g, IL-12p70, IL-17, IL-6, MCP-1 and RANTES 5 days p.i.; splenic immune cell populations had features of a controlled chronic activation before infection that was absent in WT mice, and infection resulted in ↓ inflammatory responses compared to WT mice; similar recruitment of CD4+ and CD8+ T cells with a similar activation status in the brain Waisberg et al., 2010, Proc Natl Acad Sci U S A
FcgRIIB/TLR7 Plasmodium yoelii 17XL C57BL/6 FcgRIIB-/-.yaa (SLE-susceptible), contains a duplication of TLR7 yes yes HP&A HP&A Similar Similar mortality; ↑ splenomegaly; ↓ brain and similar kidney weight Waisberg et al., 2010, Proc Natl Acad Sci U S A
Fibrinogen Plasmodium berghei ANKA CBA/J fibrinogen inhibitor yes yes CM (100%) CM (100%) N.I. Similar thrombocytopenia Senaldi et al., 1998, Cytokine
Free radicals Plasmodium chabaudi adami 556KA CBA/CaH free radical scavenger (BHA) no no N.I. N.I. Increased peak N.I. Clark et al., 1987, J Immunol
G-CSF Plasmodium berghei XAT CBA rhG-CSF no no N.I. N.I. Decreased first peak ↑ neutrophils count in peripheral blood prior to infection Waki at al., 1993, Parasitol Res
G-CSF/IFN-g Plasmodium berghei XAT CBA rhG-CSF + anti-IFN-g no no N.I. N.I. Similar N.I. Waki at al., 1993, Parasitol Res
G-CSF/TNF-a Plasmodium berghei XAT CBA rhG-CSF + anti-TNF-a no no N.I. N.I. Similar N.I. Waki at al., 1993, Parasitol Res
gd T cells Plasmodium berghei ANKA C57BL/6 d-chain-/- (gd TCR-/-) yes yes CM (53%) CM (62,5%) Similar N.I. Boubou et al., 1999, Int Immunol
gd T cells Plasmodium berghei ANKA C57BL/6 anti-gd TCR (early treatment) yes yes CM (78%) No CM N.I. N.I. Yañez et al., 1999, Infect Immun
gd T cells Plasmodium berghei ANKA C57BL/6 anti-gd TCR (late treatment) yes yes CM (67%) 67% N.I. N.I. Yañez et al., 1999, Infect Immun
gd T cells Plasmodium berghei ANKA C57BL/6 x 129 d-chain-/- (gd TCR-/-) yes yes CM (100%) CM (54%) Similar N.I. Yañez et al., 1999, Infect Immun
gd T cells Plasmodium berghei K173 C57BL/6 anti-gd TCR N.I. N.I. N.I. N.I. N.I. Similar plasma IFN-g and splenic IFN-g mRNA expression 24h p.i. Mitchell et al., 2005, Infect Immun
gd T cells Plasmodium chabaudi chabaudi AS 129/Sv x C57BL/6 d -/- TCR no no N.I. N.I. Delayed clearance N.I. Seixas et al., 1999, J Immunol
gd T cells Plasmodium chabaudi chabaudi AS C57BL/6 anti-gd TCR no N.I. N.I. N.I. Delayed clearance N.I. Seixas et al., 1999, J Immunol
gd T cells Plasmodium chabaudi chabaudi AS 129 x C57BL/6 d-chain-/- (gd TCR-/-) no no N.I. N.I. Delayed clearance Similar hypothermia, hypoglycemia and weight loss (slower recovery from weight loss); similar precursor frequency of IFN-g producing CD4+ T cells and ↑ precursor frequency of IL-4 producing CD4+ T cells 31 days p.i. to malaria antigens; earlier ↑ and greater response of CD4+ T cells providing help to B cells; ↑ malaria-specific IgG1, IgG3 and similar IgG2a, IgG2b Seixas et al., 2002, Parasite Immunol
Glucocorticoid receptor (GR) Plasmodium berghei K173 C57BL/6J dexamethasone yes yes CM No CM Decreased from day 9 No neurological symptoms or hypothermia (dose-dependent) Curfs et al., 1993, Parasitology
Glucocorticoid receptor (GR) Plasmodium berghei NK65 C57BL/6J dexamethasone (late treatment) yes yes MA-ARDS (90%) MA-ARDS (10%) Increased ↓ lung weight 10 days p.i.; ↓ IFN-g and MCP-1, ↑ TNF-a, IL-10, IL-1b and MIP-2 and similar MIF, mGCP-2/LIX, KC and MIG mRNA expression in the lungs 10 days p.i.; the mRNA expression of IP-10 and I-TAC were unsignificantly ↑; ↓ number of macrophages, CD4+ and CD8+ T cells and similar numbers of neutrophils in the lungs 10 days p.i.; ↓ number of CD4+ and CD8+ T cells in the spleen 10 days p.i.; ↓ % of Treg cells in infected spleens Van den Steen et al., 2010, Am J Crit Care Med
Glucocorticoid receptor (GR)/TNF-a Plasmodium berghei K173 C57BL/6J dexamethasone + rHu-TNF-a (↑ dose) yes yes CM No CM Decreased on day 7 No neurological symptoms (only for combinations with a low dose of dexamethasone (2,5 or 5 mg/mL) and when TNF-a was administered on day 7-8) Curfs et al., 1993, Parasitology
GM-CSF Plasmodium berghei ANKA CBA/Ca anti-GM-CSF yes yes CM (90%) CM (70%) Similar Similar mortality Grau et al., 1988, J Exp Med
GM-CSF Plasmodium berghei ANKA CBA/Ca anti-GM-CSF yes N.I. CM (80%) N.I. N.I. ↓ serum IL-6 Grau et al., 1990, J Exp Med
GM-CSF Plasmodium chabaudi chabaudi AS 129/Ola x C57BL/6 GM-CSF -/- no ♂ 75 %; ♀ 46 % Anemia Anemia Increased peak and increased recrudescences ↓ splenomegaly; ↓ leukocytosis (↓ number of macrophages, lymphocytes and similar granulocytes); similar anemia and erythropoiesis; ↑ serum TNF-a and IFN-g (↑ serum IFN-g also in uninfected KO mice compared to uninfected WT mice) Riopel et al., 2001, Infect Immun
Histamine R1 Plasmodium berghei ANKA C57BL/6J H1R inhibitor (levocetirizine) yes yes CM (80%) CM (30%) Similar Prolonged survival (2-3 weeks) only when used prophylactic; ↓ IFN-g and TNF-a brain mRNA expression 6 days p.i. Beghdadi et al., 2009, PLoS One
Histamine R1 Plasmodium berghei NK65 C57BL/6 H1R -/- yes yes N.I. N.I. Similar Prolonged survival (~3 days) Beghdadi et al., 2008, J Exp Med
Histamine R1 Plasmodium berghei NK65 C57BL/6 H1R inhibitor (levocetirizine) yes yes N.I. N.I. Similar Prolonged survival (~3 days) Beghdadi et al., 2008, J Exp Med
Histamine R2 Plasmodium berghei NK65 C57BL/6 H2R -/- yes yes N.I. N.I. Similar Prolonged survival (~3 days) Beghdadi et al., 2008, J Exp Med
Histamine R2 Plasmodium berghei NK65 C57BL/6 H2R inhibitor (cimetidine) yes yes N.I. N.I. Similar Prolonged survival (~3 days) Beghdadi et al., 2008, J Exp Med
Histamine R3 Plasmodium berghei ANKA C57BL/6J H3R agonist yes yes CM (50%) CM (25%) Similar Prolonged survival (2-3 weeks) Beghdadi et al., 2009, PLoS One
Histamine R3 Plasmodium berghei ANKA C57BL/6J x 129/Ola H3R -/- yes yes CM (100%) CM (100%) Increased Earlier death (days); Brain: earlier and ↑ Evans blue dye extravasation; ↑ number of RBC (u+p) aggregates; ↑ sequestration of CD4+, CD8+ T cells, CD11b+GR1low (macrophages) and CD11b+GR1high (Neutrophils + inflammatory macrophages) cells; ↑ levels of tele-methylhistamine (also in non-infected H3R-/- mice); ↓ mRNA expression of histidine decarboxylase (HDC) 6 days p.i. (naïve H3R -/- mice have higher levels than naïve C56BL/6J mice); ↑ plasma histamine levels 3 and 5 days p.i. (not 6 days p.i.); in vitro IL-10 and TNF-a production by P. berghei ANKA stimulated splenocytes peaked with a delay of 1 day, while IFN-g production was ↑ 4 days p.i. Beghdadi et al., 2009, PLoS One
Histamine R3 Plasmodium berghei NK65 C57BL/6 H3R inhibitor (imetit) yes yes N.I. N.I. Similar N.I. Beghdadi et al., 2008, J Exp Med
Histamine R3/R1 Plasmodium berghei ANKA H3R -/- H1R inhibitor (levocetirizine) yes yes CM (100%) CM (75%) Similar Similar IFN-g and ↓ TNF-a brain mRNA expression 6 days p.i. Beghdadi et al., 2009, PLoS One
Histamine R3/R2 Plasmodium berghei ANKA H3R -/- H2R inhibitor (cimetidine) yes yes CM (100%) CM (60%) Similar ↓ IFN-g and TNF-a brain mRNA expression 6 days p.i. Beghdadi et al., 2009, PLoS One
Histamine R4 Plasmodium berghei NK65 C57BL/6 H4R inhibitor (JNJ7777120) yes yes N.I. N.I. Similar N.I. Beghdadi et al., 2008, J Exp Med
Histidine decarboxylase (HDC) Plasmodium berghei ANKA C57BL/6 HDC -/- yes yes CM (100%) No CM Decreased on day 9 Prolonged survival (~2 weeks); no neurological symptoms; ↓ pRBC aggregates, CD4+ T cells, CD8+ T cells and ICAM-1 expression in brain microvessels; ↓ ICAM-1, IL-10, IFN-g and IL-5 mRNA, ↑ VCAM-1 mRNA and unsignificant ↓ IL-4 mRNA expression in the brain; ↓ serum IFN-g, KC and IL-5; similar serum TNF-a, IL-10, and MIP-1a; unsignificant ↓ in serum IL-6 and MCP-1; similar CD8 OT-1 and CD4 OT-2 proliferative responses after treatment with OVA Beghdadi et al., 2008, J Exp Med
Histidine decarboxylase (HDC)/CD4 Plasmodium berghei ANKA HDC -/- anti-CD4 yes yes No CM No CM Increased Prolonged survival (2-3 weeks) Beghdadi et al., 2008, J Exp Med
Histidine decarboxylase (HDC)/CD8 Plasmodium berghei ANKA HDC -/- anti-CD8 yes yes No CM No CM Increased Similar survival Beghdadi et al., 2008, J Exp Med
HMG-CoA reductase Plasmodium berghei ANKA C57BL/6 HMG-CoA reductase inhibitor (statins) yes yes CM (100%) CM (100%) Similar ↓ plasma IFN-g and similar plasma levels of MCP-1 5 days p.i.; similar plasma levels of IL-6 6 days p.i.; dose-dependent ↑ of TNF-a and IL-6 production by TLR2 and TLR4-stimulated peritoneal macrophages Helmers et al., 2009, Am J Trop Med Hyg
HMGB1 Plasmodium berghei ANKA C57BL/6 + anti-HMGB1 yes yes CM (95%) CM (75%) Similar Similar mortality; similar plasma levels of TNF, IL-12, IFN-g, IL-10 and CCL2 (MCP-1) Higgins et al., 2013, Malar J
HO-1 Plasmodium berghei ANKA DBA/2 CO gas yes yes ALI (55%) or HP&A HP&A Similar ↓ mortality from ALI (0% vs 50%); no ↑ in serum VEGF levels; no pulmonary hemorrhages or edema Epiphanio et al., 2010, PLoS Pathog
HO-1 Plasmodium berghei ANKA BALB/c HO-1 -/- (Hmox1 -/-) yes yes No CM CM (83.3%) Similar BBB breakdown; brain parenchymal hemorrhages; accumulation of activated leukocytes and red blood cells in brain microvasculature Pamplona et al., 2007, Nat Med
HO-1 Plasmodium berghei ANKA SCID HO-1 -/- (Hmox1 -/-) yes yes N.I. No CM N.I. N.I. Pamplona et al., 2007, Nat Med
HO-1 Plasmodium berghei ANKA BALB/c HO-1 inhibitor yes yes No CM CM (77.5%) Similar BBB breakdown; brain hemorrhages; accumulation of activated leukocytes and red blood cells in brain microvasculature Pamplona et al., 2007, Nat Med
HO-1 Plasmodium berghei ANKA BALB/c HO-1 inducer yes yes No CM No CM Delayed onset No neurological symptoms Pamplona et al., 2007, Nat Med
HO-1 Plasmodium berghei ANKA BALB/c heme yes yes No CM CM (100%) N.I. CM symptoms; in vitro data demonstrate that heme in the presence of ROS can disrupt BBB tight junctions Pamplona et al., 2007, Nat Med
HO-1 Plasmodium berghei ANKA C57BL/6 HO-1 inhibitor yes yes CM (100%) CM (100%) Similar Similar BBB breakdown, microvascular congestion and hemorrhages in brain; similar plasma free heme concentration (increased compared to uninfected C57BL/6 mice) Pamplona et al., 2007, Nat Med
HO-1 Plasmodium berghei ANKA C57BL/6 HO-1 inducer yes yes CM (100%) CM (10%) Delayed onset 75 % reduction of BBB disruption; no red blood cell and leukocyte sequestration in brain microvasculature; no brain hemorrhages; ↓ plasma free heme concentration Pamplona et al., 2007, Nat Med
HO-1 Plasmodium berghei ANKA C57BL/6 CO gas yes yes CM (100%) No CM Similar Protective effect was only seen with early CO treatment; 80 % reduction of BBB disruption; reduced red blood cell and leukocyte sequestration in brain microvasculature; no brain hemorrhages; ↓TNF-a, IFN-g, LT-a, ICAM-1 and VCAM-1 mRNA in brain; ↓CD8+CD69+ T cells, CD8+IFN-g+ T cells, macrophages and PMN recruitment into the brain; restored MetHb concentration; restored plasma free heme concentration to basal levels without inhibition of red blood cell lysis Pamplona et al., 2007, Nat Med
HO-1 Plasmodium berghei ANKA C57BL/6 CO gas + heme yes yes CM (100%) CM (100%) N.I. Heme reversed the protective effect of CO on CM Pamplona et al., 2007, Nat Med
HO-1 Plasmodium berghei ANKA C57BL/6 biliverdin yes yes CM (100%) CM (100%) Similar N.I. Pamplona et al., 2007, Nat Med
HO-1 Plasmodium berghei NK65 C57BL/6 heme yes yes No CM CM (100%) N.I. CM symptoms Pamplona et al., 2007, Nat Med
HO-1 Plasmodium chabaudi chabaudi AS 129 Sv x BALB/c Hmox-1 -/- no yes No liverpathology Liver pathology Similar ↑ plasma ALT, similar plasma creatinine and urea, no brain edema; accumulation of plasma protein-bound and non-protein bound heme; ↑ TBARS (lipid peroxidation derivatives in hepatocytes) Seixas et al., 2009, Proc Natl Acad Sci U S A
HO-1 Plasmodium chabaudi chabaudi AS BALB/c-SCID Hmox-1 -/- yes yes HP&A N.I. Similar Earlier mortality (days) Seixas et al., 2009, Proc Natl Acad Sci U S A
HO-1 Plasmodium chabaudi chabaudi AS DBA/2 antioxidans 80% no Liver pathology and severe anemia No liverpathology Similar ↓ plasma AST Seixas et al., 2009, Proc Natl Acad Sci U S A
HO-1 Plasmodium chabaudi chabaudi AS DBA/2 HO-1 expressing adenovirus in liver yes no Liver pathology and severe anemia No liverpathology Similar No ↑ in plasma AST and no liver portal and centrilobular vein necrosis Seixas et al., 2009, Proc Natl Acad Sci U S A
HO-1 Plasmodium yoelii 17XNL + Salmonella typhimurium C57BL/6 HO-1 inhibitor yes 100% 18h after S.t. infection yes (20% 18h after S.t. infection Bacteremia (100%) Bacteremia (~20%) Similar Infection by P. yoelii XNL decreased resistance against S. typhimurium. HO-1 inhibition restored this resistance and prevented accumulation of S. typhimurium within granulocytes resulting in prolonged survival Cunnington et al., 2012, Nat Med
HO-1/CD8 Plasmodium berghei ANKA BALB/c HO-1 -/- (Hmox1 -/-) + anti-CD8 yes yes No CM No CM N.I. N.I. Pamplona et al., 2007, Nat Med
HVEM Plasmodium berghei ANKA C57BL/6 anti-HVEM yes yes CM (90%) CM (90%) Similar Similar neurologic symptoms Randall et al., 2008, J Immunol
Hydrogen sulfide gas (HS) Plasmodium berghei ANKA C57BL/6J + NaHS (fast-releasing donor of HS) or GYY4137 (slow-releasing donor of HS) yes yes CM (100%) CM (100%) Similar Similar levels of free plasma thiols DellaValle et al., 2013, PLoS One
IDO-1 Plasmodium berghei ANKA C57BL/6 IDO-1 -/- yes yes CM (100%) CM (100%) Similar Similar histopathology; ↓ IDO-2 mRNA expression in brain (also in non-infected animals → IDO-2 in close proximity to IDO-1, and probably partly affected by gene knock out procedure); no ↑ tryptophan dioxygenase (Tdo) mRNA expression in brain; ↓ brain kynurenic acid (KA) (similar t non-infected IDO-1 -/- mice); ↓ brain quinolinic acid (QA) (but only slightly higher than non-infected IDO-1 -/- mice); ↓ brain picolinic acid (PA) (but significantly ↑ than non-infected IDO-1 -/- mice) Miu et al, 2009, Int J Parasitol
IDO-1 Plasmodium berghei ANKA C57BL/6 kynurenine-3-hydroxilase inhibitor (i.p. vs p.o.) yes yes CM (100%) CM (60% i.p. or 75% p.o.) Decreased (i.p.) or similar (p.o.) No neurologic symptoms; prolonged survival (~ 2 weeks); ↓ brain PA (also ↓ in mice that developed fatal CM, but less pronounced); similar KA and QA levels in brain Miu et al, 2009, Int J Parasitol
Ifit1 Plasmodium berghei ANKA C57BL/6 Ifit1 -/- yes yes CM (100%) CM (100%) N.I. N.I. Berghout et al., 2013, PLoS Pathog
IFN-a Plasmodium berghei ANKA C57BL/6J rHu-IFN-a yes yes CM (87%) CM (6%) Delayed onset and decreased Prolonged survival (~ 1 week): parasitemia increased when IFN-a treatment was abrogated; ↓ leukocytes in cerebral vessels and spleen; ↓ ICAM-1 in brain; ↓ serum TNF-a and↑ serum IFN-g; survival was prolonged by blood transfusion; ↓ reticulocytosis; similar anemia Vigário et al., 2007, J Immunol
IFN-a/IFN-g Plasmodium berghei ANKA C57BL/6J rHu-IFN-a + anti- IFN-g yes yes CM N.I. Decreased The inhibitory effect of IFN-a was partially abrogated Vigário et al., 2007, J Immunol
IFN-b Plasmodium berghei ANKA C57BL/6J rIFN-b yes yes CM (80%) CM (40%) (at the end of observation day 10) Similar ↓ BBB leakage, ↓ brain inflammatory cell infiltrates and improved vascular integrity 5 days p.i.; ↓ plasma MIG, TNF-a, IFNg, ↑ plasma IP-10 and similar plasma sICAM-1; ↓ MIG protein and ↑ IP-10 protein in the brain 5 days p.i.; ↓ MIG, ICAM-1 and ↑ IP-10 mRNA in the brain 5 days p.i.; ↓CD3+CD4+ and CD3+CD8+ T cells in the brain 6 days p.i.; ↓ T cells CXCR3 expression in the spleen 6 days p.i.; ↓ CXCR3 mRNA expression in the brain 6 days p.i. Morell et al., 2011, Infect Immun
IFN-g Plasmodium berghei ANKA C57BL/6 IFN-g -/- N.I. N.I. N.I. N.I. N.I. ↓ ICAM-1 and similar P-selectin protein expression in brain and lungs Bauer et al., 2002, Microcirculation
IFN-g Plasmodium berghei ANKA C57BL/6 IFN-g -/- yes yes CM (100%) No CM N.I. N.I. Berghout et al., 2013, PLoS Pathog
IFN-g Plasmodium berghei ANKA CBA/Ca anti-IFN-g yes yes CM (87,5%) CM (10-23,5%) Similar Prolonged survival (1-2 weeks); no neurological symptoms; no protection when administered just before onset of symptoms (day 7);↓ serum TNF-a; similar mononuclear cell infiltration in spleen and lymph nodes; no sequestration of macrophages, T cells or pRBC in the brain Grau et al., 1989, Proc Natl Acad Sci U S A
IFN-g Plasmodium berghei ANKA CBA/Ca anti-IFN-g yes N.I. CM (80%) N.I. N.I. ↓ serum IL-6; similar serum IgG Grau et al., 1990, J Exp Med
IFN-g Plasmodium berghei ANKA N.I. IFN-g -/- yes yes CM No CM N.I. No ↑ Indoleamine 2,3-dioxygenase-1 (IDO-1) mRNA expression in the brain ; no IDO immunoreactivity in the endothelium of non-productive tissue; similar IDO staining in epididymal tissue Hansen et al., 2004, Int J Parasitol
IFN-g Plasmodium berghei ANKA C57BL/6J IFN-g -/- yes yes CM no Similar No neurologic symptoms; ↑ levels (normal values) of [31P]-containing metabolites (phosphocreatinine (PCr), and PCr:PME), ↑ levels of b-ATP, similar levels (normal values) of phosphomonoesters (PME), and ↓ levels (normal values) of inorganic phosphate (Pi), Pi:b-ATP and Pi:PCr in brain 6-7 days p.i.; normal lactate, glutamate, GABA, aspartate, alanine, NAA and glutamine metabolite pool sizes in brain (compared with uninfected IFN-g -/- mice); no ↓ brain net flux of 13C from D-[1-13C]glucose into metabolic intermediates associated with Krebs cycle (normal compared to uninfected IFN-g -/- mice), except for Ala C3 which did not change upon infection Parekh et al., 2006, Int J Parasitol
IFN-g Plasmodium berghei ANKA C57BL/6 IFN-g -/- yes yes CM (96,5%) No CM N.I. No ↑ brain IDO activity Sanni et al., 1998, Am J Pathol
IFN-g Plasmodium berghei ANKA BALB/c IFN-g -/- yes yes No CM N.I. Similar ↓ mRNA expression of chemokines (MCP-1, RANTES, MIP-1b, MIG, IP-10, I-TAC) and adhesion molecules (ICAM-1, LFA-1, P-selectin, VCAM-1, PECAM-1) and abrogated IP-10 protein expression in the brain Van den Steen et al., 2008, Eur J Immunol
IFN-g Plasmodium berghei ANKA C57BL/6J anti-IFN-g yes yes CM N.I. Similar N.I. Vigário et al., 2007, J Immunol
IFN-g Plasmodium berghei ANKA 129 x C57BL/6 IFN-g -/- yes yes CM (58%) No CM N.I. N.I. Yañez et al., 1996, J Immunol
IFN-g Plasmodium berghei K173 C57BL/6 IFN-g -/- N.I. N.I. N.I. N.I. N.I. No ↑ IDO and similar IL-10, IL-12 and IL-18 mRNA expression 24h p.i. in the spleen Mitchell et al., 2005, Infect Immun
IFN-g Plasmodium berghei NK65 BALB/c IFN-g -/- yes yes N.I. N.I. Similar Similar mortality Ishih et al., 2008, Southeast Asian J Trop Med Public Health
IFN-g Plasmodium berghei NK65 CBA/JNCrj anti-IFN-g yes yes N.I. N.I. Similar Prolonged survival (~ 1 week) Waki et al., 1992, Immunology
IFN-g Plasmodium berghei NK65 C57BL/6 anti-IFN-g yes yes Liver pathology Liver pathology Similar Prolonged survival (~ 1 week) Yoshimoto et al., 1998, J Immunol
IFN-g Plasmodium berghei XAT CBA/JNCrj anti-IFN-g no yes N.I. N.I. Increased N.I. Waki et al., 1992, Immunology
IFN-g Plasmodium berghei XAT C57BL/6 IFN-g -/- no yes N.I. N.I. No parasite clearance ↓ phagocytic activity by splenic macrophages; similar total IgG; ↓ IgG2a Yoneto et al., 2001, J Immunol
IFN-g Plasmodium berghei XAT CBA/JNCrj anti-IFN-g no yes N.I. N.I. Increased and no clearance N.I. Yoshimoto et al., 1998, J Infect Dis
IFN-g Plasmodium berghei XAT CBA/JNCrj rIFN-g no no N.I. N.I. Delayed onset and no second peak N.I. Yoshimoto et al., 1998, J Infect Dis

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