|
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 |
Link |
|
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 |
Link |
|
Fas |
Plasmodium berghei ANKA |
C57BL/6 |
Fas -/- (lpr) |
yes |
yes |
CM (100%) |
CM (100%) |
N.I. |
N.I. |
Nitcheu et al., 2003, J Immunol |
Link |
|
Fas |
Plasmodium berghei ANKA |
C57BL/6 |
Fas -/- (lpr) |
yes |
yes |
CM |
CM (50%) |
Similar |
Heterozygotes not different from WT |
Ohno et al., 2005, Immunogenetics |
Link |
|
Fas |
Plasmodium berghei ANKA |
CBA/N |
Fas -/- (lpr) |
yes |
yes |
CM |
CM (50%) |
Similar |
Heterozygotes not different from WT |
Ohno et al., 2005, Immunogenetics |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
Fas |
Plasmodium yoelii 17XNL |
C57BL/6 |
Fas -/- (lpr) |
no |
no |
None |
None |
Increased peak and delayed clearance |
N.I. |
Ohno et al., 2005, Immunogenetics |
Link |
|
Fas |
Plasmodium yoelii 17XNL |
C3H/HeJ |
Fas -/- (lpr) |
no |
no |
None |
None |
Similar |
N.I. |
Ohno et al., 2005, Immunogenetics |
Link |
|
Fas |
Plasmodium yoelii 17XNL |
MRL/MpJ |
Fas -/- (lpr) |
no |
no |
None |
None |
Similar |
N.I. |
Ohno et al., 2005, Immunogenetics |
Link |
|
FasL |
Plasmodium berghei ANKA |
C57BL/6 |
FasL -/- (gld) |
yes |
yes |
CM (100%) |
CM (100%) |
N.I. |
N.I. |
Nitcheu et al., 2003, J Immunol |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
Fibrinogen |
Plasmodium berghei ANKA |
CBA/J |
fibrinogen inhibitor |
yes |
yes |
CM (100%) |
CM (100%) |
N.I. |
Similar thrombocytopenia |
Senaldi et al., 1998, Cytokine |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
HO-1 |
Plasmodium berghei ANKA |
C57BL/6 |
biliverdin |
yes |
yes |
CM (100%) |
CM (100%) |
Similar |
N.I. |
Pamplona et al., 2007, Nat Med |
Link |
|
HO-1 |
Plasmodium berghei NK65 |
C57BL/6 |
heme |
yes |
yes |
No CM |
CM (100%) |
N.I. |
CM symptoms |
Pamplona et al., 2007, Nat Med |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
HVEM |
Plasmodium berghei ANKA |
C57BL/6 |
anti-HVEM |
yes |
yes |
CM (90%) |
CM (90%) |
Similar |
Similar neurologic symptoms |
Randall et al., 2008, J Immunol |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
Ifit1 |
Plasmodium berghei ANKA |
C57BL/6 |
Ifit1 -/- |
yes |
yes |
CM (100%) |
CM (100%) |
N.I. |
N.I. |
Berghout et al., 2013, PLoS Pathog |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
IFN-g |
Plasmodium berghei ANKA |
C57BL/6J |
anti-IFN-g |
yes |
yes |
CM |
N.I. |
Similar |
N.I. |
Vigário et al., 2007, J Immunol |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
IFN-g |
Plasmodium berghei XAT |
CBA/JNCrj |
anti-IFN-g |
no |
yes |
N.I. |
N.I. |
Increased |
N.I. |
Waki et al., 1992, Immunology |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |