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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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
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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
IL-2/gd T cell Plasmodium yoelii 17XL DBA/2 rIL-2 + anti -gd-T cell no 71% None CM (71%) Similar Anti-gd treatment delayed (2-3 weeks) or abrogated (2/7 mice stayed healthy until the last day of observation) cerebral symptoms compared to rIL-2 treatment alone Haque et al., 2001, Am J Pathol Link
IL-23p19 Plasmodium berghei ANKA C57BL/6 IL-23p19-/- (P19KO) yes yes CM (100%) CM (100%) Similar Similar neurological symptoms Ishida et al., 2010, Biochem Biophys Res Commun Link
IL-27R Plasmodium berghei NK65 C57BL/6 IL-27R-/- (WSX-1 -/-) yes yes Liver pathology ↑ Liver pathology Decreased Earlier death (~ 1 week) and ↑ weight loss; similar mRNA expression of TNF-a, IFN-g, IL-17A, IL-2, IL-10, IL-22, IL-23 and ↓ expression of IL-12p35 in the liver 7 days p.i.; ↑ mRNA expression of IFN-g, IL-12p35 and similar expression of TNF-a, IL-17A, IL-2, IL-10, IL-22 and IL-23 in the liver 14 days p.i.; ↑plasma IFN-g and IL-17A 14 days p.i.; similar proportions and total numbers of splenic CD4+ and CD8+ T cells 7 and 14 days p.i.; ↑ % of CD4+IFNg+ T cells and similar % of CD4+TNF-a+ and CD4+IL-17A+ T cells in spleen; ↑ IFN-g, similar IL-17A, TNF-a, TBET, RORc and ↓ IL-2, IL-10, IL-4, foxp3 and GATA3 mRNA expression by splenic CD4+ T cells; similar CD4+ T cells 7 days p.i. and similar frequency, numbers and activation status of CD8+ T cells 7 and 14 days p.i. in the liver; ↑ proportion, total number and activated CD4+ T cells in the liver 14 days p.i.; ↑ % of CD4+IFNg+ and CD4+TNF-a+ T cells and similar % of CD4+IL-17A+ T cells in liver; ↑ IFN-g, similar IL-17A, TNF-a, IL-2, foxp3, TBET, GATA3, RORc and ↓ IL-10 and IL-4 mRNA expression by liver CD4+ T cells 14 days p.i.; Findlay et al., 2010, J immunol Link
IL-27R/CD4 Plasmodium berghei NK65 C57BL/6 IL-27R-/- (WSX-1 -/-) + anti-CD4 yes yes Liver pathology Similar liver pathology Similar N.I. Findlay et al., 2010, J immunol Link
IL-27R/CD8 Plasmodium berghei NK65 C57BL/6 IL-27R-/- (WSX-1 -/-) + anti-CD8 yes yes Liver pathology ↑ Liver pathology Decreased N.I. Findlay et al., 2010, J immunol Link
IL-27R/IFN-g Plasmodium berghei NK65 C57BL/6 IL-27R-/- (WSX-1 -/-) + anti-IFN-g yes yes Liver pathology ↑ Liver pathology Delayed ↑ accumulation of CD4+ T cells in the liver Findlay et al., 2010, J immunol Link
IL-27R/IFN-g/TNF-a Plasmodium berghei NK65 C57BL/6 IL-27R-/- (WSX-1 -/-) + anti-IFN-g + anti-TNF-a yes yes Liver pathology ↑ Liver pathology N.I. N.I. Findlay et al., 2010, J immunol Link
IL-27R/IL-10 Plasmodium berghei NK65 C57BL/6 IL-27R-/- (WSX-1 -/-) + rIL-10 yes yes Liver pathology ↑ Liver pathology Decreased ↑ accumulation of CD4+ T cells in the liver Findlay et al., 2010, J immunol Link
IL-27R/TNF-a Plasmodium berghei NK65 C57BL/6 IL-27R-/- (WSX-1 -/-) + anti-TNF-a yes yes Liver pathology ↑ Liver pathology Delayed ↑ accumulation of CD4+ T cells in the liver Findlay et al., 2010, J immunol Link
IL-3 Plasmodium berghei ANKA CBA/Ca anti-IL-3 yes yes CM (90%) CM (80%) similar Similar mortality Grau et al., 1988, J Exp Med Link
IL-3 Plasmodium berghei NK65 BALB/c IL-3 -/- yes yes N.I. N.I. ♂ Increased on day 8-10; ♀ Similar ♂ Prolonged survival (2-3 weeks); ♀ Similar mortality (♀ infected WT mice survive 2-3 weeks longer than ♂ infected WT mice); ↑ splenomegaly and anemia; ↑ numbers of BFU-E and CFU-E in bone marrow and spleen; similar ↑ plasma levels of GM-CSF, IL-1a, IL-1b, IL-6, IL-9, IL-10, IL-12p70, IL-13, IP-10, KC, MCP-1, M-CSF, MIP-1a, MIP-1b, and TNF; plasma levels of IFN-g and MIG are lower on day 4 and similarly ↑ on day 8 p.i., whereas G-CSF levels are higher on day 4 and 8 p.i.; ↓ % of blood neutrophils at day 8 p.i. Auclair et al., 2013, Infect Immun Link
IL-3/GM-CSF Plasmodium berghei ANKA CBA/Ca anti-IL-3 and anti-GM-CSF yes yes CM (90%) CM (13%) Similar Prolonged survival (1-2 weeks); no neurological symptoms; ↓ serum TNF-a; ↓ macrophage infiltration of white pulp (spleen) Grau et al., 1988, J Exp Med Link
IL-3/GM-CSF Plasmodium berghei ANKA CBA/Ca anti-IL-3 and anti-GM-CSF yes N.I. CM (80%) N.I. N.I. ↓ serum IL-6 Grau et al., 1990, J Exp Med Link
IL-4 Plasmodium berghei ANKA BALB/c IL-4 -/- yes 20% (infection with 400 sporozoites); yes (infection with pRBC or 800 sporozoites) N.I. N.I. No detectable parasitemia (infection with 400 sporozoites) or similar (infection with pRBC or 400 sporozoites) Surviving mice after infection with 400 sporozoites:↑ IFN-g-producing NK cells and NOS2 expression (mRNA and protein) in the liver; in uninfected and 2 days p.i.: similar numbers of CD4, CD8, NK, NKT and B cells in the liver Saeftel et al., 2004, Infect Immun Link
IL-4 Plasmodium berghei ANKA 129 x C57BL/6 IL-4 -/- yes yes CM (89%) CM (44,5%) N.I. N.I. Yañez et al., 1996, J Immunol Link
IL-4 Plasmodium berghei NK65 CBA/JNCrj anti-IL-4 yes yes N.I. N.I. Similar No effect on the outcome of infection Waki et al., 1992, Immunology Link
IL-4 Plasmodium berghei XAT CBA/JNCrj anti-IL-4 no no N.I. N.I. Similar No effect on the outcome of infection and on resistance against PbNK65 challenge Waki et al., 1992, Immunology Link
IL-4 Plasmodium chabaudi adami 556KA 129 IL-4 -/- no no N.I. N.I. Similar N.I. Van der heyde et al., 1997, Exp Parasitol Link
IL-4 Plasmodium chabaudi chabaudi AS A/J anti-IL-4 yes yes N.I. N.I. Similar Similar iNOS mRNA expression in spleen 7 days p.i.. similar NO3- levels in serum 7 days p.i.; similar spleen weight 7 days p.i. Jacobs et al. 1996, Infect Immun Link
IL-4 Plasmodium chabaudi chabaudi AS 129/Sv x C57BL/6 IL-4 -/- no no N.I. N.I. Increased recrudescences Similar IFN-g, IL-5 and ↑ IL-12 mRNA expression in spleen cells; ↓ IL-6 mRNA expression in spleen cells; similar IFN-g, IL-2, IL-10 and ↓ IL-5 and IL-6 (both only after 1 week) mRNA expression by splenic CD4+ T cells; prolonged IFN-g production by splenic CD4+ T cells (delayed switch from a Th1 to a Th2 phenotype); ↓ parasite-specific IgG1 and similar IgG2a/b production by CD4+ T cells after co-incubation with WT-derived B cells; ↓total serum IgG1, ↑ IgG2b and similar IgM, IgG2a and IgG3 1 and 6 week p.i.; ↓ total serum IgE (not detectable in uninfected KO mice); ↓ serum parasite-specific IgG1 4-6 weeks p.i.; earlier ↑ of serum parasite-specific IgG2b; ↑ serum parasite-specific IgG2a 2 weeks p.i.; similar serum parasite-specific IgM and IgG3 (IgE not detectable) Von der Weid et al., 1994, Eur J Immunol Link
IL-4 Plasmodium yoelii 17XNL 129 IL-4 -/- no no N.I. N.I. Slightly earlier clearance N.I. Van der heyde et al., 1997, Exp Parasitol Link
IL-4/NK cells Plasmodium berghei ANKA BALB/c IL-4 -/- + anti-asialo GM1 yes yes N.I. N.I. Decreased compared to anti-asialo GM1 treated WT BALB/c mice Similar IFN-g protein in the liver 3 days p.i. compared to untreated WT and ↓ compared to untreated IL-4 -/- Saeftel et al., 2004, Infect Immun Link
IL-4/NOS2 Plasmodium berghei ANKA BALB/c IL-4 -/- + NOS2 inhibitor 50% 80-100% N.I. N.I. Decreased compared to NOS2 inhibitor treated WT BALB/c mice N.I. Saeftel et al., 2004, Infect Immun Link
IL-4Ra Plasmodium berghei ANKA BALB/c IL-4Ra -/- yes 40% (infection with 400 sporozoites); yes (infection with pRBC or 800 sporozoites) N.I. N.I. No detectable parasitemia (infection with 400 sporozoites) or similar (infection with pRBC or 400 sporozoites) Surviving mice after infection with 400 sporozoites:↑ IFN-g-producing NK cells and NOS2 expression (mRNA and protein) in the liver Saeftel et al., 2004, Infect Immun Link
IL-4Ra/NK cells Plasmodium berghei ANKA BALB/c IL-4Ra -/- + anti-asialo GM1 yes yes N.I. N.I. Decreased compared to anti-asialo GM1 treated WT BALB/c mice Similar IFN-g protein in the liver 3 days p.i. compared to untreated WT and ↓ compared to untreated IL-4 -/- Saeftel et al., 2004, Infect Immun Link
IL-4Ra/NOS2 Plasmodium berghei ANKA BALB/c IL-4Ra -/- + NOS2 inhibitor yes 80-100% N.I. N.I. Decreased compared to NOS2 inhibitor treated WT BALB/c mice N.I. Saeftel et al., 2004, Infect Immun Link
IL-6 Plasmodium berghei ANKA CBA/Ca anti-IL-6 yes yes CM (80%) CM (80%) N.I. Similar IgM and ↓ IgG Grau et al., 1990, J Exp Med Link
IL-6 Plasmodium chabaudi chabaudi AS C57BL/6 rIL-6 no no N.I. N.I. Decreased second peak and earlier clearance ↑ parasite-specific IgG1, IgG2a and IgG2b and similar IgG3 serum levels Akanmori et al., 1996, Parasite Immunol Link
Immune cells Plasmodium yoelii 17XNL CBA/CaJ Adoptive transfer of unfractionated immune splenocytes no no N.I. N.I. No parasite clearance N.I. Vinetz et al., 1990, J Immunol Link
IRF-1 Plasmodium berghei ANKA C57BL/6 IRF-1 -/- yes yes CM (100%) CM (~75%) N.I. Similar numbers of CD11b+Ly6G+, Ly6C-CD11b+CD11c+MHC-II+, and CD4+ T cells, ↓ numbers of CD8+ T cells, and slightly but significantly ↑ numbers of CD11b+F4/80+ cells in the spleen at day 6 p.i.; similar serum IL-12p40 and ↓ IFN-g levels; ↓ ex vivo production of IL-12p40 by splenocytes from day 6 infected mice Berghout et al., 2013, PLoS Pathog Link
IRF-1 Plasmodium berghei ANKA C57BL/6 IRF-1 -/- yes yes CM (100%) CM (40%) Increased on day 7 Prolonged survival (until end of experiment day 13) Senaldi et al., 1999, J Immunol Link
IRF-1 Plasmodium berghei ANKA C57BL/6 IRF-1 -/- yes 25% (at the end of observation day 23) N.I. N.I. Delayed onset and decreased peak Prolonged survival (1-2 weeks); no detectable NOS2 mRNA expression in brain or NO2- in serum; ↓ IFN-g mRNA in liver, spleen and kidneys Tan et al., 1999, Infect Immun Link
IRF-1 Plasmodium berghei ANKA C57BL/6 IRF-1 -/- yes 25% (at the end of observation day 23) N.I. N.I. Delayed onset and decreased peak Prolonged survival (1-2 weeks); IL-10 mRNA was ↑ on day 4 and ↓ on day 11 after infection in liver and spleen and ↓ on day 8, 11 in the kidneys; TNF-a mRNA expression was undetectable throughout the course of infection Tan et al., 2000, Parasite Immunol Link
IRF-1/IL-12 Plasmodium berghei ANKA C57BL/6 IRF-1 -/- + rIL-12 yes yes N.I. N.I. Delayed onset and decreased peak Earlier death (days); no detectable NOS2 mRNA expression in brain or NO2- in serum; ↑ IFN-g production by ConA-stimulated spleen cells and in serum; ↑ IFN-g mRNA expression in brain, liver, spleen and kidney Tan et al., 1999, Infect Immun Link
IRF-1/IL-12 Plasmodium berghei ANKA C57BL/6 IRF-1 -/- + rIL-12 yes yes N.I. N.I. Delayed onset and decreased peak Earlier death (days); IL-10 mRNA expression was similar on day 4 and unsignificantly ↓ on day 8 p.i. in the liver, ↑ at day 4 and similar at day 8 p.i. in the spleen and similar 8 days p.i. in the kidneys; TNF-a mRNA expression was undetectable throughout the course of infection Tan et al., 1999, Infect Immun Link
IRF8 Plasmodium berghei ANKA C57BL/6 x C3H/HeJ IRF8 -/- (BXH2) yes yes CM (100%) No CM Similar until d9, followed by rapid increase No BBB leakage; no infiltration of CD4+ and CD8+ T cells, CD11b+Ly6G+ granulocytes or monocytes in the brain; ↑ numbers of CD11b+Ly6G+ and CD11b+F4/80+ cells, ↓ numbers of Ly6C-CD11b+CD11c+MHC-II+ and CD8+ T cells, and similar numbers of CD4+ T cells in the spleen at day 6 p.i.; ↓ serum IL-12p40 and IFN-g levels; ↓ ex vivo production of IL-12p40 and IFN-g by splenocytes from day 6 infected mice Berghout et al., 2013, PLoS Pathog Link
IRF8 Plasmodium berghei ANKA C57BL/6 x C3H/HeJ IRF8 +/- [BXH2 x B6]F1 yes yes CM (100%) CM (~50%) Similar No infiltration of CD4+ and CD8+ T cells, CD11b+Ly6G+ granulocytes or monocytes in the brain; similar numbers of CD11b+Ly6G+, CD11b+F4/80+, Ly6C-CD11b+CD11c+MHC-II+, and CD4+ T cells, and ↓ numbers of CD8+ T cells in the spleen at day 6 p.i.; ↓ serum IL-12p40 and IFN-g levels; ↓ ex vivo production of IL-12p40 and IFN-g by splenocytes from day 6 infected mice Berghout et al., 2013, PLoS Pathog Link
Irgm1 Plasmodium berghei ANKA C57BL/6 Irgm1 -/- yes yes CM (100%) CM (100%) N.I. N.I. Berghout et al., 2013, PLoS Pathog Link
Isg15 Plasmodium berghei ANKA C57BL/6 Isg15 -/- yes yes CM (100%) CM (100%) N.I. N.I. Berghout et al., 2013, PLoS Pathog Link
Jak3 Plasmodium berghei ANKA C57BL/6 Jak3 -/- yes 50% (at the end of observation day 18) CM (100%) No CM N.I. N.I. Berghout et al., 2013, PLoS Pathog Link
Kynurenine-3-hydroxylase Plasmodium berghei ANKA C57BL/6J kynurenine-3-hydroxylase inhibitor yes none at the end of the observation perion day 21 CM No CM Similar No neurologic symptoms; prolonged survival (~ 2 weeks); ↓ PA, similar QA and ↑ KA and AA levels in brain; ↑ KA:QA ratio; ↓ MIP-1a in brain Clark et al., 2005, Infect Immun Link
LAG-3 Plasmodium yoelii 17XNL C57BL/6 anti-LAG-3 no no N.I. N.I. Similar N.I. Butler et al., 2012, Nat Immunol Link
LIGHT Plasmodium berghei ANKA C57BL/6 LIGHT -/- yes yes CM (100%) CM (100%) Decreased Similar neurologic symptoms Randall et al., 2008, J Immunol Link
LIGHT Plasmodium berghei ANKA C57BL/6J LIGHT -/- yes yes CM (100%) CM (100%) N.I. Similar neurologic symptoms Togbe et al., 2008, PLoS One Link
LMP7 Plasmodium yoelii 17NL C57BL/6 LMP7 -/- No No N.I. N.I. Decreased peak and faster clearance N.I. Duan et al., 2013, PLoS One Link
LMP7 Plasmodium yoelii 17XL C57BL/6 LMP7 -/- yes (100%) yes (40%) N.I. N.I. Improved clearance Similar proportion of CD69+CD4+ and CD69+CD8+ T cells, similar proportion of IFN-g+CD4+ T cells, ↓ in IFN-g+CD8+ T cells, similar splenic IFN-g mRNA, ↓ DC activation, similar phagocytosis capacity of macrophages, ↑ susceptibility of iRBC to be phagoyctosed Duan et al., 2013, PLoS One Link
LT Plasmodium berghei ANKA N.I. LT -/- yes yes CM No CM N.I. Similar indoleamine 2,3-dioxygenase-1 mRNA expression in the brain Hansen et al., 2004, Int J Parasitol Link
LTa Plasmodium berghei ANKA C57BL/6 LTa -/- yes yes CM (100%) No CM Similar Prolonged survival (days); no neurological symptoms; ↓ serum NO3-; serum IFN-g non-significantly decreased; ↓ ICAM-1 on vascular endothelial cells in the brain Engwerda et al., 2002, J Exp Med Link
LTa Plasmodium berghei ANKA C57BL/6J LTa -/- yes yes CM No CM N.I. No neurologic symptoms; ↑ levels (normal values) of [31P]-containing metabolites (phosphocreatinine (PCr), b-ATP and PCr:PME), 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.; ↑ lactate, GABA and aspartate, and normal glutamate, alanine, NAA and glutamine metabolite pool sizes in brain (compared with uninfected LT-a -/- mice), however uninfected LT-a -/- mice had significantly different metabolite levels compared to uninfected WT, IFN-g -/-and TNF-a -/- mice, and brain lactate levels were ↑ but not to the same level as infected WT mice; no ↓ brain net flux of 13C from D-[1-13C]glucose into metabolic intermediates associated with Krebs cycle (normal compared to uninfected LT-a -/- mice), except for Ala C3 which did not change upon infection Parekh et al., 2006, Int J Parasitol Link
LTa Plasmodium berghei ANKA C57BL/6 LTa -/- yes yes CM (100%) CM (25%) N.I. No neurological symptoms; similar thrombocytopenia and neutrophilia; ↓ anemia and lymphopenia; ↓ ICAM-1 in brain; ↓ inflammation and edema and similar parasite sequestration in lung; similar hemozoin deposition and parasite sequestration in liver Togbe et al., 2007, Am J Pathol Link
LTa Plasmodium berghei ANKA C57BL/6J LTa -/- yes yes CM (100%) CM (10- 20%) Increased No neurologic symptoms; anemia Togbe et al., 2008, PLoS One Link
LTa Plasmodium chabaudi chabaudi AS C57BL/6 LT-a -/- no no Anemia Anemia Similar Delayed serum IFN-g and TNF-a; similar anemia and Ig titers Clark et al., 2007, Parasite Immunol Link
LTab Plasmodium berghei ANKA C57BL/6J LTab -/- yes yes CM (100%) No CM N.I. No neurologic symptoms: normal bloodflow and brain morphology, no brain swelling or edema, no mononuclear cell sequestration or hemorrhaging; lung pathology: ↓ pRBC sequestration and similar thickening of alveolar septae Togbe et al., 2008, PLoS One Link
LTb Plasmodium berghei ANKA C57BL/6J LTb -/- yes yes CM (100%) CM (70%) Increased Neurological symptoms were delayed (days); ↓ CD54+CD8+ and CD69+CD8+ T cells in brain; anemia Togbe et al., 2008, PLoS One Link
LTbR Plasmodium berghei ANKA C57BL/6 anti-LTbR yes yes CM (80%) No CM Delayed onset Prolonged survival (~ 2 weeks) only when administered before infection and 4 days p.i. (no protection with a single injection); no neurological symptoms; ↓ whole body parasite burden (PBAluc bioluminescence); ↓ parasite, macrophage and CD8+ T cell accumulation in perfused brains; similar IFN-g production by splenic NK and CD8+ T cells 3 days p.i.; similar MHCII, CD80, CD86 and CD40 expression by splenic conventional DC (cDC); similar proliferation, IFN-g and TNF-a production by parasite-specific splenic CD4+ T cells; ↓ serum TNF-a, IL-6, IFN-g and IL-10 7 days p.i.; similar annexin V staining and intracellular levels of bcl-2 in T cells, macrophages or DCs; expansion of splenic macrophages (CD11b+ Ly6C+) (also in noninfected, anti-LTbR treated mice); similar Ag uptake and processing by cDC and macrophages; similar uptake of GFP-transgenic PbA by macrophages Randall et al., 2008, J Immunol Link
LTbR Plasmodium berghei ANKA C57BL/6J LTbR -/- yes yes CM (100%) No CM Increased No neurologic symptoms: normal bloodflow and brain morphology, no brain swelling or edema, no mononuclear cell sequestration or hemorrhaging; ↓ perforin+CD8+, CD54+CD8+ and CD69+CD8+ T cells in brain; lung pathology: ↓ pRBC sequestration and similar thickening of alveolar septae; similar thrombocytopenia; no platelet adherence to cerebrovascular endothelium; similar ↓ in peripheral lymphocytes; anemia; lethal irradiation of LTbR KO or WT mice and subsequent reconstitution with bone marrow from WT or LTbR KO mice could not abolish or confer protection, respectively Togbe et al., 2008, PLoS One Link
LTbR Plasmodium chabaudi chabaudi AS C57BL/6 LTbR -/- ♂ yes ♂ yes N.I. N.I. Similar Similar reticulocytosis and anemia; castration protects WT mice but not LTbR -/- deficient mice from a lethal infection Krücken et al., 2005, Parasite Immunol Link
LTbR Plasmodium chabaudi chabaudi AS C57BL/6 LTbR -/- ♀24% ♀ 3 % N.I. N.I. Similar Earlier increase of reticulocytosis; shorter period of anemia; similar numbers of CD4+, CD8+, B220+ and F4/80+ cells in spleen; mice became susceptible after treatment with testosterone Wunderlich et al., 2005, Microbes Infect Link
LTbR/testosterone Plasmodium chabaudi chabaudi AS LTbR -/- (C57BL/6) testosterone ♀3% ♀ yes N.I. N.I. Increased peak, no clearance Delayed reticulocytosis and similar anemia; similar numbers of CD4+, CD8+, B220+ and F4/80+ cells in spleen;↑ IFN-g, IP-10, MCP-1, CD71, TIMP3, CTGF, BST1 and CTLA4 mRNA expression in the spleen, similar serum bilirubin, LDH, AST, ALT and ↓ AP; ↓ CCL5 and ↑ CCL2, CXCL10, CXCL9 PAI1, NF-IL3A and TIMP3 liver RNA Wunderlich et al., 2005, Microbes Infect Link
Lymphocytes Plasmodium berghei ANKA C57BL/6 RAG1-/- N.I. N.I. N.I. N.I. N.I. ↓ (brain) and similar (lungs) ICAM-1 protein expression; ↓ P-selectin protein expression in brain and lungs Bauer et al., 2002, Microcirculation Link
Lymphocytes Plasmodium berghei ANKA MF1 RAG2 -/- (no mature T/B cells) yes yes CM (60-80%) No CM similar Prolonged survival (> 30 days); no neurological symptoms Miyakoda et al., 2008, J Immunol Link
Lymphocytes Plasmodium berghei ANKA C57BL/6 RAG2 -/- (no mature T/B cells) yes yes CM (100%) No CM N.I. Prolonged survival (2-3 weeks) Nitcheu et al., 2003, J Immunol Link
Lymphocytes Plasmodium berghei ANKA RAG2 -/- adoptively transfered CD8 + T cells from WT mice yes yes No CM CM (100%) N.I. N.I. Nitcheu et al., 2003, J Immunol Link
Lymphocytes Plasmodium berghei ANKA RAG2 -/- adoptively transfered CD8 + T cells from PFP -/- mice yes yes No CM No CM N.I. N.I. Nitcheu et al., 2003, J Immunol Link
Lymphocytes Plasmodium berghei ANKA C57BL/6-SCID-SzJ no T/B cells yes yes CM (100%) No CM N.I. No neurological symptoms Yañez et al., 1996, J Immunol Link
Lymphocytes Plasmodium berghei NK65 SCID (BALB/c were used as controls) no T/B cells yes N.I. Liver pathology No liverpathology N.I. ↓ serum GPT (ALT); no liver injury Adachi et al., 2001, J Immunol Link
Lymphocytes Plasmodium berghei NK65 SCID (C57BL/6 were used as controls) no T/B cells yes N.I. Liver pathology No liverpathology N.I. No liver injury; no cytotoxicity by hepatic NK cells against hepatocytes Adachi et al., 2004, Int Immunol Link
Lymphocytes Plasmodium chabaudi adami 556KA C57BL/6 x CBA anti-m-chain from birth (no B cells) no no N.I. N.I. Developed a chronic low parasitemia Resistant to a secondary infection with P. chabaudi adami 556 KA or P. vinckei, but not to P. yoelii 17XNL or P. berghei Grun et al., 1981, Nature Link
Lymphocytes Plasmodium chabaudi adami 556KA BALB/c-nu/+ BALB/c-nu/nu no yes N.I. N.I. Developed a high persistent parasitemia Resistant to a secondary infection with P. chabaudi adami 556 KA or P. vinckei, but not to P. yoelii 17XNL or P. berghei Grun et al., 1981, Nature Link
Lymphocytes Plasmodium chabaudi adami 556KA CB-17-SCID (genetically histocompatible with BALB/cHSD) Adoptive transfer of immune T cells yes no N.I. N.I. Spontaneous decline and clearance Resolved infection; developed high levels of splenic CD4+ and gd T cells Van der Heyde et al., 1993, J Immunol Link
Lymphocytes Plasmodium chabaudi adami 556KA CB-17-SCID (genetically histocompatible with BALB/cHSD) Adoptive transfer of immune T cells + anti-CD8 yes no N.I. N.I. Spontaneous decline and clearance Resolved infection; developed high levels of splenic CD4+ and gd T cells Van der Heyde et al., 1993, J Immunol Link
Lymphocytes Plasmodium chabaudi adami 556KA CB-17-SCID (genetically histocompatible with BALB/cHSD) Adoptive transfer of immune T cells + anti-CD4 yes yes N.I. N.I. Similar Developed low levels of splenic CD4+ and gd T cells Van der Heyde et al., 1993, J Immunol Link
Lymphocytes Plasmodium chabaudi adami 556KA BALB/cHSD anti-m-chain from birth no no N.I. N.I. Developed a chronic low parasitemia ↑ gd T cells (mostly CD4-CD8-) and similar numbers of ab T cells in spleen Van der heyde et al., 1996, J Leukoc Biol Link
Lymphocytes Plasmodium chabaudi adami 556KA C57BL/6 x 129 m-BCR -/- (m-MT) no N.I. N.I. N.I. Developed a chronic low parasitemia ↑ gd T cells (mostly CD4-CD8-) and similar numbers of ab T cells in spleen Van der heyde et al., 1996, J Leukoc Biol Link
Lymphocytes Plasmodium chabaudi adami 556KA C57BL/6J x 129 JH-gene segment -/- (JHD -/-) no no N.I. N.I. Slightly delayed and developed a chronic, low parasitemia ↑ gd T cells (mostly CD4-CD8-) and similar numbers of ab T cells in spleen; ↑ gd T cells and similar ab T cells in cell-cycle during acute parasitemia (determines the proliferative response); treatment with immune serum ↓ parasitemia Van der heyde et al., 1996, J Leukoc Biol Link
Lymphocytes Plasmodium chabaudi AS C57BL/6 RAG1-/- No N.I. N.I. N.I. Increased on day 9 ↓ sequestration in livers (day 5 and day 9 p.i.) and spleen (day 5 p.i.), but not in the lungs; ↓ serum ALT levels; ; similar albumin levels in BAL fluid; similar tubular dilatation and plasma creatinine levels and ↑ plasma urea levels Brugat et al., 2013, Cell Microbiol Link
Lymphocytes Plasmodium vinckei petteri CR C57BL/6J x 129 JH-gene segment -/- (JHD -/-) no no N.I. N.I. N.I. ↑ gd T cells and similar numbers of CD4+ ab T cells in spleen Van der heyde et al., 1996, J Leukoc Biol Link
Lymphocytes Plasmodium yoelii 17XL BALB/c-SCID no T/B cells yes yes N.I. N.I. Similar N.I. Hisaeda et al., 2004, Nat Med Link
Lymphocytes Plasmodium yoelii 17XNL BALB/c SCID (No T/B cells) no yes N.I. N.I. Earlier increase, no clearance N.I. Hisaeda et al., 2004, Nat Med Link
Mannose receptors Plasmodium chabaudi AS C57BL/6 mannan no no N.I. N.I. Similar ↓ phagocytosis of pRBCs and free merozoites Su et al., 2002, J Infect Dis Link
meso 2,3-dimercaptosuccinic acid (DMSA) Plasmodium chabaudi chabaudi AS A/J + DMSA (structural analogue of CysH, prophylactic treatment) ♂ yes (100%); ♀ yes (25%) ♂ yes (100%); ♀ yes (25%) N.I. N.I. Similar N.I. Min-Oo et al., 2010, Exp Parasitol Link
MHC-II Plasmodium berghei ANKA C57BL/6 IA-b -/- (↓MHC-II → ↓ CD4) N.I. N.I. N.I. N.I. Similar on day 5 Prolonged survival (days) Nie et al., 2009, PLoS Pathog Link
MHC-II Plasmodium berghei ANKA C57BL/6 x 129 A -/- (↓MHC-II → ↓ CD4) + anti-NK1.1 yes yes CM (91%) CM (100%) N.I. N.I. Yañez et al., 1996, J Immunol Link
MHC-II Plasmodium berghei ANKA C57BL/6 x 129 A -/- or Ii -/- (↓MHC-II → ↓ CD4) yes yes CM (84%) CM (44%) Similar Similar hematocrit levels and neurological symptoms Yañez et al., 1996, J Immunol Link
MHC-II Plasmodium berghei NK65 C57BL/6 MHC-II -/-(↓ CD4) yes yes Liver pathology Liver pathology N.I. Similar liver injury, serum ALT levels and hepatic DX5+CD3+ cells; ↓ cytotoxicity by hepatic lymphocytes against hepatocytes Adachi et al., 2004, Int Immunol Link
MHC-II/CD4 Plasmodium berghei ANKA C57BL/6 x 129 A -/- (↓MHC-II → ↓ CD4) + anti-CD4 yes yes CM (50%) No CM N.I. N.I. Yañez et al., 1996, J Immunol Link
MHC-II/CD4 Plasmodium berghei ANKA C57BL/6 x 129 A -/- or Ii -/- (↓MHC-II → ↓ CD4) + anti-CD4 yes N.I. CM (84%) No CM N.I. N.I. Yañez et al., 1996, J Immunol Link
MHC-II/IP-10 Plasmodium berghei ANKA C57BL/6 IA-b -/- (↓MHC-II → ↓ CD4) + anti-IP-10 N.I. N.I. N.I. N.I. Similar on day 5 Prolonged survival (days) Nie et al., 2009, PLoS Pathog Link
Microparticle (MP) Plasmodium berghei ANKA CBA/J MP formation inhibitor (pantethine) yes 60-70% (at the end of observation day 20) CM (100%) No CM Similar No neurological symptoms; prolonged survival (1-3 weeks); no↑ in circulating MP; ↓ plasma TNF-a; ↓ dose or treatment for a shorter period led to partial protection; ↓ PS-exposure on platelet and RBC membrane; ↓ platelet binding to fibrinogen after incubation with thrombin; ↓ platelet adhesion to collagen; preserved redox status as observed by ↓ amount of –SH moieties on the platelet membrane Penet et al., 2008, Proc Natl Acad Sci U S A Link
MMP-9 Plasmodium berghei ANKA C57BL/6J MMP-9 -/- yes yes CM (100%) CM (90%) Similar N.I. Van den Steen et al., 2006, Lab Invest Link
MMP/TACE Plasmodium berghei ANKA C57BL/6J Broad-spectrum MMP/TACE inhibitor yes yes CM (100%) CM (100%) Similar Mice died 1 day later Van den Steen et al., 2006, Lab Invest Link
Monocyte/Macrophages Plasmodium berghei ANKA C57BL/6J Chemical depletion of macrophages from spleen and liver (early treatment) (lip-Cl2MDP) yes yes CM (100%) CM (50-75%) N.I. No cerebral symptoms; no hypothermia Curfs et al., 1993, Parasitology Link
Monocyte/Macrophages Plasmodium berghei ANKA C57BL/6J Chemical depletion of macrophages from spleen and liver (late treatment) (lip-Cl2MDP) yes yes CM (100%) CM (100%) N.I. N.I. Curfs et al., 1993, Parasitology Link
Monocyte/Macrophages Plasmodium berghei K173 C57BL/6J Chemical depletion of macrophages from spleen and liver (early treatment) (lip-Cl2MDP) yes yes CM (100%) CM (30-40%) N.I. No cerebral symptoms; no hypothermia Curfs et al., 1993, Parasitology Link
Monocyte/Macrophages Plasmodium chabaudi AS A/J Chemical activation of macrophages (early treatment) (liposomal MDP-GDP) 100% 100% N.I. N.I. Increased N.I. Stevenson et al., 1989, Parasite Immunol Link
Monocyte/Macrophages Plasmodium chabaudi AS A/J Chemical activation of macrophages (late treatment) (liposomal MDP-GDP) 100% 25% N.I. N.I. Decreased N.I. Stevenson et al., 1989, Parasite Immunol Link
Monocyte/Macrophages Plasmodium chabaudi AS C57BL/6 Chemical depletion of macrophages (silica) no 40-70% N.I. N.I. Delayed clearance (exp1); increased peak (exp2) N.I. Stevenson et al., 1989, Parasite Immunol Link
MyD88 Plasmodium berghei ANKA C57BL/6 MyD88 -/- yes yes CM (90%) CM (46.15%) Similar No red blood cell and leukocyte sequestration in brain microvasculature; no endothelial cell detachment; ↓ hemozoin accumulation in brain vessels; ↓ granzyme B, CCL3 and lipocalin 2 mRNA in brain; ↓ CD4+, CD8+, CCR5+, CD11c+, B220+ and NK1.1+ cells in brain; ↓ serum IL-12p40, IFN-g and TNF-a Coban et al., 2007, Int Immunol Link
MyD88 Plasmodium berghei ANKA C57BL/6 MyD88 -/- yes yes CM (100%) CM (100%) Similar Similar neurologic symptoms, thrombocytopenia, neutrophilia and lymphopenia; ↓ anemia; similar ICAM-1 in brain; similar inflammation, edema and parasite sequestration in lung; similar hemozoin deposition and parasite sequestration in liver Togbe et al., 2007, Am J Pathol Link
MyD88 Plasmodium berghei NK65 BALB/c MyD88 -/- yes yes Liver pathology No liverpathology Similar Similar serum IL-18; ↓ serum IL-12p40 and GPT (ALT); no liver injury; similar infiltration of lymphocytes in liver Adachi et al., 2001, J Immunol Link

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