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
MyD88 Plasmodium chabaudi AS C57BL/6 MyD88 -/- no no N.I. N.I. Similar Similar up-regulation of CD40, CD86 and MHC class II, decreased production of TNF-a and IL-12p70, no degradation of IkB-a and no translocation of NF-kB to the nucleus after incubation of MyD88 -/- DCs with P. berghei or P. chabaudi schizonts; Decreased expression of CD40, CD80 and CD86 on splenic DCs isolated from P. berghei-infected mice 6 days p.i. and P. chabaudi-infected mice 7 days p.i. Seixas et al., 2009, Eur J Immunol
MyD88 Plasmodium chabaudi chabaudi AS C57BL/6 MyD88 -/- no no N.I. N.I. Similar Less severe hypothermia and no weight loss; resistant to a secondary infection; ↑ IgG1 and similar IgG2a levels; ↓ TNF-a and IFN-g and similar MCP-1 production by splenocytes (in vitro) and in the serum (in vivo) 8 days p.i.; ↓ production of IL-1a, IL-6 (only by DC), TNF-a and IL-12 by CD11b+ macrophages and CD11c+ DC cells in spleen; similar expression of CD40 and CD86 by DC (similar maturation status), ↓ number of ab TCR+, CD4+ and NK cells producing IFN-g and TNF-a; ↓ % op CD25+ and CD69+ CD4+ T cells Franklin et al., 2007, Microbes Infect
MyD88 Plasmodium yoelii 17XNL N.I. MyD88 -/- no 37.5% N.I. N.I. Increased ↓ serum IL-12p40 and similar IL-18 6 days p.i.; similar number of CD62Llow+CD4+ and CD69+CD4+ T cells in the spleen 6 days p.i.; no difference in [3H]thymidine uptake upon stimulation of splenocytes with anti-CD3; ↓ production of IL-12p40, IFN-g and similar IL-10 after stimulation of splenocytes isolated 6 days p.i. with anti-CD3 (similar IFN-g and IL-10 production compared to IL-18 -/-) Cramer et al., 2008, Microbes Infect
NADPH oxidase Plasmodium berghei ANKA 129/Sv x C57BL/6 gp91phox -/- (no ROS) yes yes CM (100%) CM (100%) Faster increase N.I. Sanni et al., 1999, J Infect Dis
NADPH oxidase Plasmodium chabaudi adami 556KA C57BL/6 p47phox-/- (no ROI produced by the NADPH oxidase pathway) no no N.I. N.I. Similar Putative function of ROI was not masked by antibody-mediated immunity as B cell deficient p47phox -/- mice displayed similar parasitemias Gillman et al., 2004, Infect Immun
NADPH oxidase/B cells Plasmodium chabaudi adami 556KA JH -/- (C57BL/6J x 129) p47phox-/- (no ROI produced by the NADPH oxidase pathway) no no N.I. N.I. Similar N.I. Gillman et al., 2004, Infect Immun
NADPH oxidase/NOS2 Plasmodium chabaudi adami 556KA C57BL/6 p47phox-/- x NOS2-/- no no N.I. N.I. Similar N.I. Gillman et al., 2004, Infect Immun
NADPH oxidase/NOS2/XO Plasmodium chabaudi adami 556KA p47phox-/- x NOS2-/- (C57BL/6) xanthine oxidase inhibitor no no N.I. N.I. Non-significantly increased peak N.I. Gillman et al., 2004, Infect Immun
NADPH oxidase/XO Plasmodium chabaudi adami 556KA p47phox -/- (C57BL/6) xanthine oxidase inhibitor no no N.I. N.I. Increased peak N.I. Gillman et al., 2004, Infect Immun
NADPH oxidase/XO/B cells Plasmodium chabaudi adami 556KA JH -/- x p47phox -/- (C57BL/6J x 129) xanthine oxidase inhibitor no no N.I. N.I. Increased peak N.I. Gillman et al., 2004, Infect Immun
Neutrophils + eosinophils Plasmodium berghei ANKA C57BL/6 anti-Gr-1 (late treatment) yes yes CM (100%) CM (100%) N.I. N.I. Belnoue et al., 2003, Infect Immun
Neutrophils + eosinophils Plasmodium berghei ANKA CBA/NSlc anti-Gr-1 (day - 1) yes yes CM (100%) CM (10%) Similar Prolonged survival (~ 2 weeks); ↓ cerebral hemorrhages; ↓ sequestration of monocytes and pRBCs; similar anemia; PMNs start to increase again 4 days p.i. in peripheral blood; similar TNF-a, IFN-g, IL-10 mRNA and ↓ IL-2, IL-12p40, IL-4 mRNA in the spleen; IL-4 and IL-10 undetectable in brain; no IL-12p40 and ↓ IL-2, IFN-g and TNF-a mRNA in the brain Chen et al., 2000, Clin Exp Immunol
Neutrophils + eosinophils Plasmodium berghei ANKA CBA/NSlc anti-Gr-1 (late treatment) yes yes CM (100%) CM (100%) N.I. N.I. Chen et al., 2000, Clin Exp Immunol
Neutrophils + eosinophils Plasmodium berghei ANKA CBA/Ca anti-Gr-1 (late treatment) yes yes CM (85-90%) CM (40%) Similar Delayed mortality; Blood: ↓ blood leukocytes; no neutrophils; similar serum TNF-a, IgG and platelet count; Brain: ↓ edema; ↓ monocytes sequestration; ↑ micro-hemorrhages; ↓ injected aggregated albumine; similar platelet sequestration; Lung: ↓ edema; ↓ myeloperoxidase activity (neutrophil enzyme); ↓ monocytes sequestration; similar platelet sequestration; Other organs: no effect on liver pathology; ↑ micro-hemorrhages in skin Senaldi et al., 1994, Infect Immun
NK cells Plasmodium berghei ANKA C57BL/6 anti-asialo GM1 yes 80% (at the end of observation day 15) CM (100%) No CM Increased on day 6 Prolonged survival (~ 1 week); similar naïve and activated CD4+ and CD8+ T cells in spleen; ↓ sequestration of CD4+ and CD8+ T cells in the brain; ↓ CXCR3+ T cells in the spleen; ↓ chemotactic response of T cells to IP-10 and T cell migration to the brain could be partially restored by adoptive transfer of IFN-g +/+ NK cells but not by IFN-g -/- NK cells; adoptively transferred IFN-g +/+, but not IFN-g -/- NK cells, were able to migrate into the brain of infected animals Hansen et al., 2007, J Immunol
NK cells Plasmodium berghei ANKA BALB/c anti-asialo GM1 yes yes N.I. N.I. Similar Earlier death (1-2 weeks); similar IFN-g protein in the liver 3 days p.i. Saeftel et al., 2004, Infect Immun
NK cells Plasmodium berghei K173 C57BL/6 anti-asialo GM1 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
NK cells Plasmodium berghei NK65 C57BL/6 Beige mutation (bg/ bg) (defect in NK cell cytotoxicity) yes yes Liver pathology Liver pathology N.I. Similar liver injury and serum ALT levels Adachi et al., 2004, Int Immunol
NK cells Plasmodium berghei NK65 C57BL/6 Beige mutation (bg/ bg) (defect in NK cell cytotoxicity) yes yes N.I. N.I. More abrupt incline Earlier mortality (~ 1 week) Solomon et al., 1985, Immunol Lett
NK cells Plasmodium chabaudi chabaudi AS C57BL/6 anti-asialo GM1 no no N.I. N.I. Increased peak and increased recrudescences N.I. Mohan et al., 1997, J Immunol
NK cells Plasmodium chabaudi chabaudi AS C57BL/6-bg/+ Beige mutation (bg/ bg) (defect in NK cell cytotoxicity) no no N.I. N.I. Similar ↓ in vitro NK cell cytotoxicity and similar IFN-g and TNF-a secretion by enriched NK cells Mohan et al., 1997, J Immunol
NK cells Plasmodium chabaudi chabaudi AS C57BL/6-bg/+ Bg/bg + anti-IFN-g + anti-TNF-a no no N.I. N.I. Earlier and increased peak N.I. Mohan et al., 1997, J Immunol
NK cells Plasmodium chabaudi chabaudi AS C57BL/6-bg/+ Beige mutation (bg/ bg) (defect in NK cell cytotoxicity) 10% no N.I. N.I. N.I. N.I. Skamene et al., 1983, Parasite Immunol
NK cells Plasmodium yoelii 17XNL BALB/c x C57BL/6 anti-asialo GM1 no N.I. N.I. N.I. N.I. ↓ IFN-g and similar TNF-a protein levels in the spleen 24h p.i. De Souza et al., 1997, Infect Immun
NK/NKT cells Plasmodium berghei ANKA C57BL/6 NKC complex BALB/c (B6.BALB/c-Cmv1s) yes 90% (at the end of observation day 17) CM (100%) CM (90%) Similar N.I. Hansen et al., 2003, Immunity
NK/NKT cells Plasmodium berghei ANKA BALB/c NKC complex C57BL/6 (BALB.B6-Cmv1r) 20% (at the end of observation day 17) 50% (at the end of observation day 16) CM (20%) CM (50%) Similar Sequestration of pRBC and macrophages in cerebral vasculature; depletion of NK cells by anti-asialo GM1 treatment did not reverse the increased susceptibility to CM (40 % survival); ↑ % of CD44+Vb8+ and NK1.1+abTCR+ cells in spleen early during infection; adoptive transfer of CD44+Vb8+ NKT cells from BALB/c.B6-Cmv1r mice into BALB/c mice ↑ susceptibility to CM (33.4 %) and adoptive transfer of CD44+Vb8+ NKT cells from BALB/c mice into BALB/c.B6-Cmv1r mice ↓ susceptibility to CM (25 %); naïve CD44+Vb8+ NKT cells produced similar IL-4 and IFN-g when stimulated with anti-CD3 and ↑ IFN-g when stimulated with anti-NK1.1 (in vitro); similar proliferation and IL-4 production and no downregulation of IFN-g production later in infection when infected CD44+Vb8+ NKT cells were stimulated with a-GalCer; similar intracellular IL-4 and ↑ IFN-g production (ex vivo) by CD44+Vb8+ NKT cells; differential expression of NKC markers such as NK1.1 and members of the Ly49 gene superfamily, similar expression of NKG2A/C/E and Ly49C/I Hansen et al., 2003, Immunity
NK/NKT cells Plasmodium berghei ANKA BALB/c NKC complex C57BL/6 (BALB.B6-Cmv1r) 20% (at the end of observation day 17) 54% (at the end of observation day 16) CM (20%) CM (54%) Similar Sequestration of pRBC and macrophages in cerebral vasculature; ↑ pulmonary edema and anemia; similar serum TNF-a; ↑ serum IFN-g throughout infection and ↓ TGF-b 14 days p.i.; ↑ mRNA expression of IFN-g and IFN-g-inducible genes in spleen (eg. IFN-g inducible GTPases, chemokines,…); ↑ IgM and ↓ IgG (total and parasite specific IgG, IgG1, IgG2a, IgG2b, IgG3) titers during the second week of infection Hansen et al., 2005, Infect Immun
NK/NKT cells Plasmodium berghei ANKA C57BL/6 anti-NK1.1 yes yes CM (91%) CM (91%) N.I. N.I. Yañez et al., 1996, J Immunol
NK/NKT cells Plasmodium berghei NK65 C57BL/6 anti-NK1.1 yes yes Liver pathology Liver pathology N.I. Similar liver injury Adachi et al., 2004, Int Immunol
NKT cell Plasmodium berghei ANKA BALB/c CD1d -/- N.I. N.I. N.I. N.I. N.I. ↓ splenomegaly:↓ BrdU+B220+ cells and similar numbers of CD4+ and CD8+ T cells; ↓ proliferative response after adoptive transfer of B cells from WT mice; ↓ parasite-specific serum IgM, total IgG and IgG1 titers, ↑ IgG2a titers and similar IgG2b and IgG3; similar number of CD69+, B7-1+ and B7-2+B220+ cells in spleen; no downregulation of IFN-g and no switch towards IL-4 production by splenocytes or isolated CD4+ T cells (isolated 7 days p.i.) after in vitro stimulation with anti-CD3; ↓ anti-MSP19 antibody response 7 days after the first infection and 14 days after the second challenge Hansen et al., 2003, Eur J Immunol
NKT cell Plasmodium berghei ANKA C57BL/6 CD1d -/- yes 80% (at the end of observation day 14) CM (100%) CM (80%) Similar ↓ serum IFN-g; similar serum TNF-a; ↓ proliferative response and IFN-g production by CD4+ T cells in vitro after stimulation with parasite lysate or anti-CD3 at early time-points (day 3) and similar IL-4 production Hansen et al., 2003, Immunity
NKT cell Plasmodium berghei ANKA BALB/c CD1d -/- 20% (at the end of observation day 18) 60% (at the end of observation day 18) CM (20%) CM (60%) Similar Developed neurological symptoms; ↑ serum IFN-g and TNF-a; ↑ proliferative response and IFN-g production and similar IL-4 production by CD4+ T cells after in vitro stimulation with parasite lysate at early time-points (day 3); similar proliferative response, no downregulation of IFN-g and no switch towards IL-4 production by splenocytes or isolated CD4+ T cells after in vitro stimulation with anti-CD3 later during infection (day 7) Hansen et al., 2003, Immunity
NKT cell Plasmodium berghei K173 C57BL/6 CD1d -/- 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
Nlrc4 Plasmodium berghei ANKA C57BL/6 Nlrc4 -/- yes yes CM (100%) CM (100%) N.I. N.I. Berghout et al., 2013, PLoS Pathog
Nlrp3 Plasmodium berghei ANKA C57BL/6 Nlrp3 -/- 56% (at the end of observation day 20) 27% (at the end of observation day 20) CM (56%) CM (27%) Similar ↓ leukocyte infiltration, ↓ damaged endothelial cells and ↓ CD45-staining in brain Dostert et al., 2009, PLoS One
Nlrp3 Plasmodium berghei ANKA N.I. Nlrp3 -/- yes yes CM (100%) CM (100%) Similar Slightly delayed death (~ 2 days); similar serum levels of IFN-g, IL-10, TNF, IL-1b and IL-6; similar mRNA expression of IP-10, P-selectin and ICAM-1 in the brain; similar up-regulation of CD69 and down-regulation of CD62L on T-cells; similar frequency of IFN-g-producing CD4+ T cells Reimer et al., 2010, Eur J Immunol
Nod1Nod2 Plasmodium berghei ANKA C57BL/6 Nod1Nod2 -/- yes yes CM (100%) CM (100%) Similar Similar plasma IFN-g, IL-6 and TNF-a; ↓ plasma IL-1b, MCP-1 (CCL2) and KC (CXCL1-3) Finney et al., 2009, Am J Trop Med Hyg
NOS2 Plasmodium berghei ANKA C57BL/6 x 129Sv/Ev NOS2 -/- yes yes CM CM similar N.I. Favre et al., 1999, Parasitology
NOS2 Plasmodium berghei ANKA C57BL/6 x 129Sv/Ev NOS inhibitor yes yes CM CM similar N.I. Favre et al., 1999, Parasitology
NOS2 Plasmodium berghei ANKA C57BL/6 NOS2 -/- yes yes CM (100%) CM (100%) similar N.I. Gramaglia et al., 2006, Nat Med
NOS2 Plasmodium berghei ANKA C57BL/6 NO donor or + NO gas yes 20% (at the end of observation day 12) CM (100%) CM (20%) similar No neurological symptoms; restored cGMP brain levels; ↓ plasma IL-18, sCD40 and MMP-9; similar IL-1b, IL-6, IL-10, IFN-g and TIMP-1 Gramaglia et al., 2006, Nat Med
NOS2 Plasmodium berghei ANKA CBA/J NOS inhibitor yes yes CM (76%) CM (76%) similar N.I. Kremsner et al., 1993, Immunology
NOS2 Plasmodium berghei ANKA BALB/c NOS2 inhibitor 50% 100% N.I. N.I. Similar N.I. Saeftel et al., 2004, Infect Immun
NOS2 Plasmodium chabaudi adami 556KA C57BL/6 NOS2 -/- no no N.I. N.I. Similar Putative function of NO was not masked by antibody-mediated immunity as B cell deficient NOS2 -/- mice displayed similar parasitemias Gillman et al., 2004, Infect Immun
NOS2 Plasmodium chabaudi adami 556KA C57BL/6 NOS2 inhibitor no no N.I. N.I. Similar N.I. Van der Heyde et al., 2000, J Immunol
NOS2 Plasmodium chabaudi adami 556KA C57BL/6 NOS2 -/- no no N.I. N.I. Similar ↓ serum NOx levels 14 days p.i. Van der Heyde et al., 2000, J Immunol
NOS2 Plasmodium chabaudi chabaudi AS MF1 NOS inhibitor 10% 25% N.I. N.I. Similar Similar body weight, locomotor activity, liver size and splenomegaly Dascombe et al., 2003, Parasite Immunol
NOS2 Plasmodium chabaudi chabaudi AS C57BL/6 x 129Sv/Ev NOS inhibitor no no N.I. N.I. Similar Similar anemia; ↓ leukocytosis Favre et al., 1999, Parasitology
NOS2 Plasmodium chabaudi chabaudi AS C57BL/6 x 129Sv/Ev NOS2 -/- no no N.I. N.I. Similar Similar anemia; ↓ leukocytosis Favre et al., 1999, Parasitology
NOS2 Plasmodium chabaudi chabaudi AS NIH NOS inhibitor no no N.I. N.I. Increased peak N.I. Taylor-Robinson et al., 1993, Science
NOS2 Plasmodium yoelii 17XL C57BL/6J NOS inhibitor yes 80% (at the end of observation day 15) N.I. N.I. Similar No effect on the outcome of infection Kobayashi et al., 2000, J Vet Med Sci
NOS2/B cells Plasmodium chabaudi adami 556KA JH -/- (C57BL/6J x 129) NOS2 -/- no no N.I. N.I. Similar N.I. Gillman et al., 2004, Infect Immun
NOS2/B cells Plasmodium chabaudi adami 556KA JHD (129 x C57BL/6) NOS2 -/- no no N.I. N.I. Similar ↓ serum NOx levels on day 10 and 20 p.i. Van der Heyde et al., 2000, J Immunol
NOS2/XO Plasmodium chabaudi adami 556KA NOS2 -/- (C57BL/6) xanthine oxidase inhibitor no no N.I. N.I. Increased peak N.I. Gillman et al., 2004, Infect Immun
NOS2/XO/B cells Plasmodium chabaudi adami 556KA JH -/- x NOS2 -/- (C57BL/6J x 129) xanthine oxidase inhibitor no no N.I. N.I. Increased peak N.I. Gillman et al., 2004, Infect Immun
NOS3 Plasmodium berghei ANKA C57BL/6 NOS3 -/- yes yes CM (100%) CM (100%) similar N.I. Gramaglia et al., 2006, Nat Med
NOS3 Plasmodium chabaudi adami 556KA C57BL/6 NOS3 -/- no no N.I. N.I. Similar Similar serum NOx levels 14 days p.i. Van der Heyde et al., 2000, J Immunol
P2X7R Plasmodium berghei ANKA N.I. P2X7R -/- yes yes CM (100%) CM (100%) N.I. N.I. Reimer et al., 2010, Eur J Immunol
PAFR Plasmodium berghei ANKA C57BL/6 PAFR -/- yes yes CM (100%) CM (40%) Similar Recovered from weight loss at the time point when WT mice succumbed; ↓ microvascular obstruction; no cerebral hemorrhages; similar leukocyte rolling and adhesion; ↓ pro-IL-1b and CCL2/MCP-1 and similar ICAM-1, VCAM-1, IL-10, CXCL10/IP-10 and CCL5/RANTES mRNA levels in the brain; ↓ brain caspase-3 activation and ↓ caspase-3+ cells; no edema; ↓ CD8+ T cells and less decrease in CD62L on CD8+ T cells Lacerda-Queiroz et al., 2012, Am J Pathol
PAFR Plasmodium berghei ANKA C57BL/6 PAFR selective antagonist (UK74,505) yes yes CM (100%) CM (40-75%) Similar Recovered from weight loss at the time point when WT mice succumbed Lacerda-Queiroz et al., 2012, Am J Pathol
Pantethine Plasmodium chabaudi chabaudi AS A/J + pantethine (structural analogue of CysH, prophylactic treatment) ♂ yes (100%); ♀ yes (70%) ♂ yes (100%); ♀ yes (60%) N.I. N.I. Similar N.I. Min-Oo et al., 2010, Exp Parasitol
PARP-1 Plasmodium berghei ANKA C57BL/6 x 129/Sv PARP -/- yes yes CM (95%) CM (80%) N.I. N.I. Hempel et al., 2011, Am J Pathol
PD-L1 Plasmodium berghei ANKA BALB/cAnNCrl anti-PD-L1 yes yes CM (~30%) CM (91%) Similar ↑ numbers of CD8+ T cells in the brain; ↑ frequency of brain petechial hemorrhages; ↑ proportion of vessels plugged with iRBCs; ↑ numbers of pigmented (parasite-containing) macrophages in the liver; ↑ whole body, head and isolated brain parasite burdens (↑ bioluminescence of luciferase-expressing parasites);↑ proportion of activated CD8+ T cells in the spleen; ↑ plasma IFN-g, MCP-1/CCL2 and IL-10 and similar TNF and IL-6; ↑ secretion of IFN-g by stimulated CD4+ T cells and ↑ IFN-g secretion by stimulated CD8+ T cells; Hafalla et al., 2012, PLoS Pathog
PD-L1 Plasmodium yoelii 17XNL C57BL/6 anti-PD-L1 no no N.I. N.I. Decreased N.I. Butler et al., 2012, Nat Immunol
PD-L1/CD4 Plasmodium berghei ANKA BALB/cAnNCrl anti-PD-L1 + anti-CD4 yes yes CM (~30%) CM (100%) N.I. N.I. Hafalla et al., 2012, PLoS Pathog
PD-L1/CD8 Plasmodium berghei ANKA BALB/cAnNCrl anti-PD-L1 + anti-CD8 yes yes CM (~30%) No CM N.I. N.I. Hafalla et al., 2012, PLoS Pathog
PD-L1/IFN-g Plasmodium berghei ANKA BALB/cAnNCrl anti-PD-L1 + anti-IFN-g yes yes CM (~30%) No CM N.I. Hafalla et al., 2012, PLoS Pathog
PD-L1/LAG-3 Plasmodium chabaudi C57BL/6 anti-PD-L1 + anti-LAG-3 no no N.I. N.I. Similar peak and no recrudescences (complete parasite elimination) N.I. Butler et al., 2012, Nat Immunol
PD-L1/LAG-3 Plasmodium yoelii 17XNL C57BL/6 anti-PD-L1 + anti-LAG-3 no no N.I. N.I. Decreased PD-L1 and LAG-3 synergistically decrease parasitemia; ↑ numbers of splenic parasite-specific CD4+ and CD8+ T cells, IFN-g+TNF+ and IFN-g+IL-2+ parasite-specific CD4+ and CD8+ T cells, follicular CD4+ T cells, plasmablasts, CD19+B220+ B cells, PNA+ germinal-center B cells; improved splenic architecture with preservation of IgM+ B cell follicles and enhanced PNA+ germinal center formation; ↑ titers of MSP-1(19)-specific IgGs after immunization with a human malaria vaccine candidate MSP-1(19); ↑ parasite clearance in mice recieving serum from PD-L1 and LAG-3 depleted mice when mice were challenged with P. yoelii Butler et al., 2012, Nat Immunol
PD-L1/LAG-3 Plasmodium yoelii 17XNL Swiss Webster anti-PD-L1 + anti-LAG-3 no no N.I. N.I. Decreased N.I. Butler et al., 2012, Nat Immunol
PD-L1/TNF Plasmodium berghei ANKA BALB/cAnNCrl anti-PD-L1 + anti-TNF yes yes CM (~30%) CM (~80%) N.I. Hafalla et al., 2012, PLoS Pathog
PD-L2 Plasmodium berghei ANKA BALB/cAnNCrl anti-PD-L2 yes yes CM (<20%) CM (<20%) Similar N.I. Hafalla et al., 2012, PLoS Pathog
Perforin (PFP) Plasmodium berghei ANKA C57BL/6 PFP -/- yes yes CM (100%) No CM N.I. Prolonged survival (2-3 weeks); similar edema, sequestration of pRBCs and accumulation of CD44+CD62L- CD4 and CD8 T cells in the brain; adoptively transfered splenocytes from infected WT mice migrate to the brain and induce CM; adoptively transfered CD8+ cells from infected WT mice, but not from infected PFP -/- mice, induce CM in RAG2 -/- mice (lack peripheral T and B cells); ↓ cytolytic activity of IFN-g producing CD8+ cells; similar expression of CXCR3, CXCR4, CCR2 and CCR5 on CD8+ cells Nitcheu et al., 2003, J Immunol
Perforin (PFP) Plasmodium berghei ANKA N.I. PFP -/- yes yes CM No CM Similar No brain edema or hemorrhages; similar sequestration of leukocytes in brain microvasculature; similar endothelial staining of fibrinogen but no leakage of fibrinogen in brain parenchyma; ↓ mRNA expression of granzyme B, ↑ mRNA expression of CD8 and similar mRNA expression of CD4 (no increase) in brain; no TUNEL/isolectin double positive cells in retinae Potter et al., 2006, Int J Parasitol
Perforin (PFP) Plasmodium berghei NK65 C57BL/6 PFP -/- yes N.I. Liver pathology No liverpathology N.I. ↓ serum GPT (ALT); no liver injury; similar lymphocyte infiltration in liver Adachi et al., 2001, J Immunol
PGI2 Plasmodium berghei ANKA CBA/Ca synthetic PGI2 analog yes yes CM (75%) CM (8%) Similar No neurological symptoms; prolonged survival (~ 2-3 weeks), ↓ serum TNF-a (only 3 mice/group → no statistics performed) Sliwa et al., 1991, Infect Immun
Plasmacytoid DCs Plasmodium chabaudi AS 129 Sv/Ev anti-pDC (120G8) no no N.I. N.I. Similar Similar weight loss and hypothermia Voisine et al., 2010, Int J Parasitol
Plasmin Plasmodium berghei ANKA C57BL/6J aprotinin (serine protease inhibitor) yes 40% (at the end of observation day 15) CM (100%) CM (40%) N.I. Prolonged survival (until end of observation); ↓ thrombocytopenia Piguet et al., 2000, Infect Immun
Platelets Plasmodium berghei ANKA C57BL/6J + anti-platelet (anti-GPIb) (day -1) + serum amyloid P (rSAP) yes yes CM (100%) CM (100%) N.I. Delayed mortality (days) compared to the platelet depleted mice without rSAP treatment Aggrey et al., 2013, J Immunol
Platelets Plasmodium berghei ANKA C57BL/6J + anti-platelet (anti-GPIb) or platelet inhibitor (Clopidogrel) (day -1) yes yes CM (80-100%) CM (80-100%) Increased on day 5 ↓ plasma concentrations of serum amyloids A and P and IL-1b Aggrey et al., 2013, J Immunol
Platelets Plasmodium berghei ANKA C57BL/6J + anti-platelet (anti-GPIb) or platelet inhibitor (Clopidogrel) (day 1) yes yes CM (80-100%) CM (20%) N.I. Similar plasma concentrations of serum amyloids A and P and IL-1b Aggrey et al., 2013, J Immunol
Platelets Plasmodium berghei ANKA CBA/J anti-platelet yes yes CM (97%) CM (31,5%) N.I. Anti-platelet (LFA-1+) antibodies prevented CM even when administered on day 6 Grau et al., 1993, Eur Cytokine Netw
Platelets Plasmodium berghei ANKA C57BL/6 anti-platelet (anti-GPIb) or platelet inhibitors (acetylsalisyllic acid (ASA) or Clopidogrel (day 1) 60% (at the end of observation day 10) 20% (at the end of observation day 10) CM (60%) CM (20%) N.I. Anti-platelet therapy starting 3 days p.i. did not improve survival; mice treated with ASA had ↓ number of brain T cell infiltrates compared to control (non-infected) mice Srivastava et al., 2008, Cell Host Microbe
Scavenger receptors Plasmodium chabaudi AS C57BL/6 Scavenger receptor blockage by Poly(I) no no N.I. N.I. Earlier increase in parasitemia, increased peak and similar parasite clearance ↓ phagocytosis of free merozoites (only slight ↓in pRBC phagocytosis); similar serum IL-12p40 Su et al., 2002, J Infect Dis
sFLT1 (sVEGFR) Plasmodium berghei ANKA DBA/2 sFLT1-expressing adenovirusses yes yes ALI (70%) or HP&A (30%) ALI (17%) or HP&A (83%) N.I. ↓ mortality from ALI (18% vs 70%); ↑ sFLT1 expression; ↓ serum VEGF Epiphanio et al., 2010, PLoS Pathog
SOCS1 Plasmodium berghei ANKA C57BL/6 SOCS1 -/- yes yes CM (80%) No CM Similar Prolonged survival (2-3 days); no neurologic symptoms; lympocytic infiltrates in muscle and lungs; ↓ splenic cellularity; ↓CD4:CD8 T cell ratio compared to WT mice, but similar as in uninfected KO mice Bullen et al., 2003, Parasite Immunol
SOCS1 Plasmodium berghei ANKA C57BL/6 SOCS1 +/- yes yes CM (80%) CM (80%) Similar Similar neurological symptoms Bullen et al., 2003, Parasite Immunol
SOCS2 Plasmodium berghei ANKA C57BL/6 SOCS2 -/- yes yes CM (100%) CM (100%) N.I. N.I. Bullen et al., 2003, Parasite Immunol
Stat1 Plasmodium berghei ANKA C57BL/6 Stat1 -/- yes yes CM (100%) No CM N.I. N.I. Berghout et al., 2013, PLoS Pathog
T cells Plasmodium berghei ANKA BALB/c-nu/+ Nude mice (nu/nu): no thymus thus no mature T cells yes yes CM (70%) No CM A less abrupt incline Prolonged survival (~ 2 weeks); slower progression of anemia; similar parasite-specific and total IgM titers; delayed and ↓ parasite-specific and total IgG titers; ↑ serum C3 levels; ↓ immune complexes in serum Finley et al., 1982, J Immunol
T cells Plasmodium berghei ANKA CBA/J, CBA/Ca AT x BM (no thymus: no mature T cells) yes yes CM (90%) No CM Similar ↓ serum IgM and IgG; protection was abrogated after reconstitution with CD4+ T cells (partially restored IgM + IgG levels), but not after reconstitution with CD8+ T cells Grau et al., 1986, J Immunol
T cells Plasmodium berghei K173 C57BL/6J Thymectomy + anti-CD4 (early treatment) yes yes CM (90%) CM (25%) Similar N.I. Hermsen et al., 1997, Parasitology
T cells Plasmodium berghei K173 C57BL/10 Thymectomy + anti-CD4 (early treatment) yes yes CM (100%) CM (27%) Similar N.I. Hermsen et al., 1997, Parasitology
T cells Plasmodium chabaudi chabaudi AS C57BL/6NCrlBR anti-Thy-1 no 36.4% N.I. N.I. Increased peak and developed a high, persistent parasitemia The high, persistent parasitemia coincided with the high level of reticulocytosis Podoba et al., 1991, Infect Immun
T cells Plasmodium chabaudi chabaudi AS NIH Thymectomy + anti-CD4 no 75-100% N.I. N.I. Developed a high persistent parasitemia Serum NO3- low and similar to untreated and uninfected mice Taylor-Robinson et al., 1993, Science
T cells Plasmodium chabaudi chabaudi AS NIH, thymectomy + anti-CD4 CD4+ splenic T cells from normal mice 75-100% 40% N.I. N.I. Similar ↑ serum NO3- during peak parasitemia Taylor-Robinson et al., 1993, Science
T cells Plasmodium chabaudi chabaudi AS NIH, thymectomy + anti-CD4 TH1 cells from infected mice 75-100% no N.I. N.I. Similar peak, parasite clearance after 1 recrudescence ↑ serum NO3- during peak parasitemia; ↑ IgM; detection of IgG2a during peak and recrudescent parasitemia; anti-IgG treatment ↑ recrudescent parasitemia Taylor-Robinson et al., 1993, Science
T cells Plasmodium chabaudi chabaudi AS NIH, thymectomy + anti-CD4 TH1 cells from infected mice + NOS inhibitor 75-100% 75-100% N.I. N.I. Similar Similar (No NO3- in serum during peak parasitemia); increase in IgG2a levels abrogated compared to Th1 reconstituted mice without NOS inhibitor; IgM not affected by NOS inhibitor Taylor-Robinson et al., 1993, Science
T cells Plasmodium chabaudi chabaudi AS NIH, thymectomy + anti-CD4 TH2 cells from infected mice 75-100% no N.I. N.I. Similar peak, parasite clearance after 1 recrudescence Similar (No NO3- in serum during peak parasitemia); no ↑ IgM and detection of IgG1 during peak and recrudescent parasitemia; survival was abrogated by anti-IgG and anti-IgG1 treatment, but not by treatment with anti-IgG2a Taylor-Robinson et al., 1993, Science
T cells Plasmodium chabaudi chabaudi AS NIH, thymectomy + anti-CD4 TH2 cells from infected mice + NOS inhibitor 75-100% no N.I. N.I. Similar peak, parasite clearance after 1 recrudescence Similar (No NO3- in serum during peak parasitemia); similar IgG1 levels compared to Th2 reconstituted mice without NOS inhibitor Taylor-Robinson et al., 1993, Science

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