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
IFN-g Plasmodium chabaudi adami 556KA CBA/CaH rIFN-g no no N.I. N.I. Delayed onset and decreased peak Resistant to secondary infection Clark et al., 1987, J Immunol
IFN-g Plasmodium chabaudi adami 556KA 129/Sv x C57BL/6 (WT = 129/Ola) IFN-g -/- no no N.I. N.I. Delayed clearance N.I. Van der heyde et al., 1997, Exp Parasitol
IFN-g Plasmodium chabaudi chabaudi AS DBA/2 anti-IFN-g yes yes N.I. N.I. Increased peak Similar body weight and body temperature Cross et al., 1998, Exp Parasitol
IFN-g Plasmodium chabaudi chabaudi AS B10.D2 anti-IFN-g no no N.I. N.I. Increased peak ↓ body weight and body temperature Cross et al., 1998, Exp Parasitol
IFN-g Plasmodium chabaudi chabaudi AS C57BL/6 anti-IFN-g no no 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
IFN-g Plasmodium chabaudi chabaudi AS C57BL/6 rIFN-g no no N.I. N.I. Decreased peak N.I. Meding et al., 1990, Infect Immun
IFN-g Plasmodium chabaudi chabaudi AS C57BL/6 anti-IFN-g no no N.I. N.I. Increased peak N.I. Meding et al., 1990, Infect Immun
IFN-g Plasmodium chabaudi chabaudi AS C57BL/6 IFN-g -/- no ♂ 100 %; ♀ 40 % N.I. N.I. ♂: increased peak ♀: increased peak and increased recrudescences ↓serum TNF-a, IL-12p70 and NO; ↓ splenic macrophages, NK cells and T cells (only in ♂); similar splenic B cells and Mac-1+ cells; ↓parasite-specific IgM, IgG2a, IgG3 and ↑IgG1; similar TNF-a, IL-4 and ↑ IL-10 production by spleen cells after in vitro stimulation with pRBC Su et al., 2000, Infect Immunol
IFN-g Plasmodium yoelii 17XL C57BL/6J anti-IFN-g yes yes N.I. N.I. Similar Earlier death (days) Kobayashi et al., 2000, J Vet Med Sci
IFN-g Plasmodium yoelii 17XL CBA/J rIFN-g no no N.I. N.I. Decreased peak No effect on the outcome of infection Shear et al., 1989, J Immunol
IFN-g Plasmodium yoelii 17XL SW rIFN-g yes yes N.I. N.I. Delayed onset and decreased peak Prolonged survival (days, dose-dependent); ↑ phagocytic activity and H2O2 production by peritoneal macrophages that was partially abrogated after pretreatment with anti-IFN-g Shear et al., 1989, J Immunol
IFN-g Plasmodium yoelii 17XL BALB/cByJ rIFN-g yes yes N.I. N.I. Delayed onset and decreased peak Prolonged survival (days, dose-dependent) Shear et al., 1989, J Immunol
IFN-g Plasmodium yoelii 17XNL SW rIFN-g no no N.I. N.I. Similar No effect on the outcome of infection Shear et al., 1989, J Immunol
IFN-g Plasmodium yoelii 17XNL BALB/cByJ rIFN-g no no N.I. N.I. Decreased peak No effect on the outcome of infection Shear et al., 1989, J Immunol
IFN-g Plasmodium yoelii 17XNL CBA/J rIFN-g no no N.I. N.I. Similar No effect on the outcome of infection Shear et al., 1989, J Immunol
IFN-g Plasmodium yoelii 17XNL 129/Ola x C57BL/6 (WT = 129/Ola) IFN-g -/- no no N.I. N.I. No parasite clearance in 30 days N.I. Van der heyde et al., 1997, Exp Parasitol
IFN-g/CTLA-4 Plasmodium berghei ANKA C57BL/6 IFN-g -/- + anti-CTLA-4 yes yes No CM No CM N.I. N.I. Jacobs et al., 2002, J Immunol
IFN-g/CTLA-4 Plasmodium berghei ANKA C57BL/6 IFN-g -/- + anti-CTLA-4 yes yes Moderate liver pathology Moderate liver pathology N.I. ↓ serum AST and ALT levels compared to anti-CTLA-4-treated WT (similar compared to untreated WT mice); ↓ CD4+ T cells in liver compared to untreated and anti-CTLA-4-treated WT mice (similar compared to untreated IFN-g -/-) Jacobs et al., 2004, Eur J Immunol
IFN-gR Plasmodium berghei ANKA 129/Sv/Ev x C57BL/6 (WT = 129 Sv/Ev) IFN-gR -/- yes yes CM (60-100% depending on the parasite dose used) No CM Similar/higher depending on the parasite dose used No neurological symptoms; similar anemia; ↑ serum IFN-g, TNF-a; similar IFN-g protein expression in the brain and ↑ IFN-g protein expression in the spleen; ↓ TNF-a mRNA expression in the spleen and brain; ↓ TNF-a protein expression in the brain; ↓ IL-6 and IL-10 mRNA expression in the brain; similar IL-6 mRNA expression in the spleen; similar NO in serum, brain and spleen Amani et al., 2000, Eur J Immunol
IFN-gR Plasmodium berghei ANKA DBA/1 IFN-gR -/- yes yes CM (89%) No CM 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), ↑ mRNA expression of P-selectin and abrogated IP-10 protein expression in the brain Van den Steen et al., 2008, Eur J Immunol
IFN-gR Plasmodium chabaudi adami 556KA 129/Sv/Ev x C57BL/6 IFN-gR -/- no no N.I. N.I. Delayed peak N.I. Tsuji et al., 1995, J Immunol
IFN-gR Plasmodium chabaudi AS C57BL/6 IFN-gR -/- No N.I. N.I. N.I. Increased on day 9 ↓ sequestration in livers (day 5 and day 9 p.i.), but not in spleen or lungs; ↓ serum ALT levels; similar numbers of IFN-g+ lymphocytes in the lungs 9 days p.i.; similar IgM and albumin levels in BAL fluid; similar tubular dilatation, plasma creatinine levels and plasma urea levels Brugat et al., 2013, Cell Microbiol
IFN-gR Plasmodium chabaudi chabaudi AS 129/Sv/Ev x C57BL/6 IFN-gR -/- no 77% N.I. N.I. Second peak as high as first peak First peak:↑ parasite-specific IgM, similar IgG1 and ↓ IgG2a, IgG2b and IgG3; ↓ serum NO3-; ↑ leukocytosis; similar anemia; ↓ splenomegaly; second peak: similar serum NO3-; ↑ leukocytosis and anemia; similar splenomegaly; ↑ parasite-specific IgM and IgG1 after second peak; resistant to secondary infection Favre et al., 1997, Parasite Immunol
IFN-gR Plasmodium chabaudi chabaudi AS 129/Sv/Ev x C57BL/6 IFN-gR -/- no no Anemia Anemia Prolonged acute parasitemia with second peak Similar hypoglycaemia and weight loss; more pronounced hypothermia Li et al., 1999, Infect Immun
IFN-gRa Plasmodium berghei ANKA 129P2Sv/Ev IFN-gRa -/- yes yes CM (60-100%) No CM Similar ↓ total leukocyte numbers and CD8+ T cells and similar numbers of macrophages, neutrophils and CD4+ T cells in the brain at the time of CM; ↑ numbers of total leukocytes, macrophages, CD4+ and CD8+ T cells and ↓ numbers of neutrophils in the lungs at the time of CM; no pulmonary edema; ↓ mRNA expression of MIP-1a/CCL3, RANTES/CCL5, IP-10/CXCL10, CCR2 and CCR1 and similar MCP-1/CCL2, CCR5 and CXCR3 in the brain; ↑ mRNA expression of MCP-1/CCL2 and IP-10/CXCL10, ↓ CCR2 and CXCR3 and similar MIP-1a/CCL3, RANTES/CCL5, CCR5 and CCR1 in the lungs; ↑ mRNA expression of MIP-1a/CCL3, IP-10/CXCL10, CCR5 and CXCR3 and similar MCP-1/CCL2, RANTES/CCL5, CCR2 and CCR1 in the spleen Belnoue et al., 2008, Parasite Immunol
IFNabR Plasmodium chabaudi AS 129 Sv/Ev IFNabR -/- no no N.I. N.I. Similar Increased weight loss and hypothermia Voisine et al., 2010, Int J Parasitol
IFNaR1 Plasmodium berghei ANKA C57BL/6 IFNaR1 -/- yes yes CM (~90%) CM (~25%) Increased on day 6-7 Prolonged survival (2-3 weeks); no neurological symptoms; no BBB leakage; less intravascular accumulation of mononuclear cells; no endothelial cell disruption or hemorrhagic lesions; similar parasite accumulation and CD3 expression in the brain; delayed kinetics of TNF and IL-10 mRNA expression in the brain; ↓ numbers of CD8+, CD8+GrB+, and CD8+IFN-g+ cells in the spleen at baseline in uninfected mice, similar numbers in the spleen at day 5 p.i., and ↓ numbers in the brain at day 6 p.i. Ball et al., 2013, J Immunol
IFNaR1 Plasmodium berghei ANKA IFNaR1 + adoptive transfer of total splenocytes from C57BL/6 mice that had recieved irradiated pRBCs yes yes CM (~25%) CM (~75%) N.I. N.I. Ball et al., 2013, J Immunol
IFNaR1 Plasmodium berghei ANKA IFNaR1 -/- + adoptive transfer of splenic CD8+ cells from C57BL/6 mice that had recieved irradiated pRBCs yes yes No CM CM (100%) Similar BBB leakage (↑ compared to infected IFNaR1-/- that not recieved cells); CD8+, CD8+GrB+, and CD8+IFN-g+ cells were found in the brain Ball et al., 2013, J Immunol
IFNaR1 Plasmodium berghei ANKA IFNaR1 -/- + adoptive transfer of splenocytes depleted of CD8+ cells from C57BL/6 mice that had recieved irradiated pRBCs yes yes No CM No CM Similar No BBB leakage (similar compared to infected IFNaR1-/- that not recieved cells); CD8+, CD8+GrB+, and CD8+IFN-g+ cells were found in the brain Ball et al., 2013, J Immunol
IFNaR1 Plasmodium berghei ANKA IFNaR1 -/- + adoptive transfer of splenic CD8+ cells from IFNaR1-/- mice that had recieved irradiated pRBCs yes yes No CM CM (~25%) Similar N.I. Ball et al., 2013, J Immunol
IL-10 Plasmodium berghei ANKA BALB/c anti-IL-10 yes yes HP&A HP&A similar Similar mortality; ↑ TNF-a Kossodo et al., 1997, Immunology
IL-10 Plasmodium berghei ANKA CBA/J rIL-10 yes yes CM (100%) CM (38.6 %) similar Prolonged survival (days-weeks); no neurological symptoms; similar TNF-a Kossodo et al., 1997, Immunology
IL-10 Plasmodium berghei ANKA 129 x C57BL/6 IL-10 -/- yes yes CM (89%) CM (100%) N.I. N.I. Yañez et al., 1996, J Immunol
IL-10 Plasmodium berghei NK65 C57BL/6 IL-10 -/- yes yes Liver pathology ↑ Liver pathology Decreased Similar weight loss (↓ compared to IL-27R -/- mice); ↑ liverpathology (similar compared to IL-27R -/- mice); ↑ numbers of total splenic CD4+ T cells and similar numbers of liver-infiltrating CD4+ T cells 14 days p.i. (↑ numbers of total splenic CD4+ T cells and ↓ numbers of liver-infiltrating CD4+ T cells compared to IL-27R -/- mice) Findlay et al., 2010; J immunol
IL-10 Plasmodium chabaudi adami 556KA 129/Ola x C57BL/6 IL-10 -/- no no N.I. N.I. Similar Similar number of splenic gd T cells Van der heyde et al., 1996, J Leukoc Biol
IL-10 Plasmodium chabaudi adami 556KA 129/Ola x C57BL/6 (WT = 129/Ola) IL-10 -/- no no N.I. N.I. Similar N.I. Van der heyde et al., 1997, Exp Parasitol
IL-10 Plasmodium chabaudi AS C57BL/6 IL-10 -/- No N.I. N.I. N.I. Similar ↑ sequestration in the spleen (day 9 p.i.) and in the liver (day 5 and day 9 p.i. although not significantly), but not in the lungs; similar serum ALT levels; ↑ numbers of IFN-g+ lymphocytes in the lungs 9 days p.i.; ↑ IgM and albumin levels in BAL fluid; ↑ tubular dilatation, plasma creatinine levels and plasma urea levels Brugat et al., 2013, Cell Microbiol
IL-10 Plasmodium chabaudi chabaudi AS 129/Sv x C57BL/6 IL-10 -/- no ♀ 50 %; ♂ no Anemia Anemia Similar ↑ mortality;↑ hypothermia, hypoglycemia and weight loss in ♀ Li et al., 1999, Infect Immun
IL-10 Plasmodium chabaudi chabaudi AS C57BL/6 IL-10 -/- no ♀ 30 %; ♂ no Anemia Anemia Similar ↑ mortality;↑ hypothermia, hypoglycemia and weight loss in ♀; ↑ plasma TNF-a and IFN-g; ↑ TNF-a, IFN-g, IL-12p40 and NOS2 mRNA in spleen Li et al., 1999, Infect Immun
IL-10 Plasmodium chabaudi chabaudi AS C57BL/6 IL-10 -/- no ♀ 66 % Anemia N.I. Similar ↑ mortality; surviving mice had ↓ hypothermia and hypoglycaemia, similar anemia and weight loss; ↑ serum TGF-b Li et al., 2003, Infect Immun
IL-10 Plasmodium chabaudi chabaudi AS C57BL/6 IL-10 -/- no ♀ 70 % Anemia CM (♀ 70 %) Similar ↑ parasite sequestration; cerebral edema and hemorrhages (CM?) Sanni et al., 2004, Infect Immun
IL-10 Plasmodium yoelii 17XL C57BL/6J anti-IL-10 yes 40% (at the end of observation day 25) N.I. N.I. Similar N.I. Kobayashi et al., 2000, J Vet Med Sci
IL-10 Plasmodium yoelii 17XL C57BL/6 anti-IL-10R yes yes N.I. N.I. Similar ↑ plasma IFN-g Omer et al., 2003, J Immunol
IL-10 Plasmodium yoelii 17XNL 129/Ola x C57BL/6 (WT = 129/Ola) IL-10 -/- no not in 30 days N.I. N.I. Similar N.I. Van der heyde et al., 1997, Exp Parasitol
IL-10/CD25 Plasmodium berghei ANKA C57BL/6 IL-10 -/- + anti-CD25 yes yes CM (100%) CM (100%) N.I. Delayed mortality (1-2 days); similar neurologic symptoms Amante et al., 2007, Am J Pathol
IL-10/IFN-g Plasmodium chabaudi chabaudi AS C57BL/6 IL-10 -/- + anti-IFN-g no no Anemia Anemia Increased recrudescences Similar hypothermia, hypoglycemia and weight loss compared to IL-10-/- mice Li et al., 1999, Infect Immun
IL-10/IFN-g Plasmodium chabaudi chabaudi AS 129/Sv x C57BL/6 IL-10-/- x IFN-gR-/- no no Anemia Anemia Prolonged acute parasitemia and prominent second peak Similar hypothermia, hypoglycemia, weight loss and plasma TNF-a compared to IL-10-/- mice Li et al., 1999, Infect Immun
IL-10/TGF-b Plasmodium chabaudi chabaudi AS IL-10 -/- anti-TGF-b ♀ 66 % ♀ yes (100%) N.I. N.I. Similar ↑ anemia and hypoglycemia, similar hypothermia and weight loss; ↑ plasma IFN-g and TNF-a Li et al., 2003, Infect Immun
IL-10/TNF-a Plasmodium chabaudi chabaudi AS IL-10 -/- anti-TNF-a ♀ 66 % ♀ no N.I. N.I. Increased recrudescences ↓ hypothermia, anemia, weight loss and similar hypoglycemia; similar plasma IFN-g Li et al., 2003, Infect Immun
IL-10/TNF-a Plasmodium chabaudi chabaudi AS IL-10 -/- anti-TNF-a ♀ 70 % no CM (♀ 70 %) N.I. N.I. ↓ cerebral edema and hemorrhages (50 %) Sanni et al., 2004, Infect Immun
IL-12 Plasmodium berghei ANKA C57BL/6 IL-12 -/- N.I. N.I. N.I. N.I. N.I. Similar ICAM-1 protein expression in the brain; ↓ ICAM-1 protein expression in the lung Bauer et al., 2002, Microcirculation
IL-12 Plasmodium berghei ANKA C57BL/6 rIL-12 yes 20% (at the end of observation day 23) N.I. N.I. Delayed onset and decreased peak Prolonged survival (1-2 weeks); ↑ NOS2 mRNA expression in brain 11 days p.i., in kidneys 4 days p.i. and in liver and spleen; ↑ NO2- and IFN-g production by ConA stimulated spleen cells and in serum; ↑ IFN-g mRNA expression in liver, spleen and kidney; ↑ liver pathology; ↓ IL-10 and similar TNF-a mRNA in spleen; ↑ NOS2 and similar IFN-g in brain and spleen Tan et al., 1999, Infect Immun
IL-12 Plasmodium berghei ANKA C57BL/6 rIL-12 yes 20% (at the end of observation day 23) N.I. N.I. Delayed onset and decreased peak which declined partly with subsequent increase Prolonged survival (1-2 weeks); IL-10 mRNA was ↓ on day 11 after infection in liver and spleen and ↓ on day 8, 11 in the kidneys; similar TNF-a expression in liver, spleen and kidneys Tan et al., 2000, Parasite Immunology
IL-12 Plasmodium berghei XAT CBA/JNCrj rIL-12 no no N.I. N.I. Delayed onset and no second peak ↑ IFN-g and IL-10 and ↓ IL-4 mRNA expression in the spleen; ↑ IFN-g production by unstimulated, ConA and anti-CD3 stimulated spleen cells; ↓ IL-4 production by ConA and anti-CD3 stimulated spleen cells Yoshimoto et al., 1998, J Infect Dis
IL-12 Plasmodium berghei XAT CBA/JNCrj anti-IL-12 no yes N.I. N.I. Increased and no clearance ↓ IFN-g and NOS2 and similar IL-4 and IL-10 mRNA expression in the spleen; ↓ IFN-g protein production by spleen cells Yoshimoto et al., 1998, J Infect Dis
IL-12 Plasmodium chabaudi chabaudi AS A/J rIL-12 yes no N.I. N.I. Spontaneous decline ↑ NKCC by spleen cells (maximal NKCC activity enhancement after 2 days rIL-12 treatment and ↓ NKCC activity enhancement after longer rIL-12 treatment); ↑ splenic cellularity (similar to infected C57BL/6 mice): ↑ number of CD3+, B220+ and Mac-1+ spleen cells; ↑ IFN-g and similar TNF-a production by splenic NK cells Mohan et al., 1997, J Immunol
IL-12 Plasmodium chabaudi chabaudi AS A/J rIL-12 yes yes Severe anemia Severe anemia Similar Similar anemia and reticulocytosis; rIL-12-treated splenocytes produced similar amounts of IFN-g after parasite-antigen stimulation compared to untreated splenocytes Mohan et al., 1999, Infect Immun
IL-12 Plasmodium chabaudi chabaudi AS C57BL/6 rIL-12 no 60% N.I. N.I. Decreased peak N.I. Stevenson et al., 1995, J Immunol
IL-12 Plasmodium chabaudi chabaudi AS A/J rIL-12 yes 25% N.I. N.I. Decreased peak and spontaneous decline Dose-dependant survival; ↑ production of IFN-g and similar production of IL-4 and IL-5 by spleen cells 7 days p.i.; ↑ serum IFN-g, TNF-a and NO3- Stevenson et al., 1995, J Immunol
IL-12/CD4 Plasmodium chabaudi chabaudi AS A/J rIL-12 + anti-CD4 yes yes N.I. N.I. Similar N.I. Stevenson et al., 1995, J Immunol
IL-12/chloroquine Plasmodium chabaudi chabaudi AS A/J rIL-12 + chloroquine yes no Severe anemia None Decreased peak ↓ anemia, ↑ erythropoiesis and reticulocytosis; combined therapy induced ↑ IFN-g production by parasite antigen stimulated splenocytes; resistant to secondary infection due to ↑ parasite-specific IgG levels Mohan et al., 1999, Infect Immun
IL-12/CTLA-4 Plasmodium berghei ANKA C57BL/6 IL-12p40 -/- + anti-CTLA-4 yes yes No CM No CM N.I. N.I. Jacobs et al., 2002, J Immunol
IL-12/CTLA-4 Plasmodium berghei ANKA C57BL/6 IL-12p40 -/- + anti-CTLA-4 yes yes Moderate liver pathology Moderate liver pathology N.I. ↓ serum AST and ALT levels compared to anti-CTLA-4-treated WT (similar compared to untreated WT mice); ↓ CD4+ T cells in liver compared to anti-CTLA-4-treated WT mice (similar compared to IL-12 -/- and untreated WT mice) Jacobs et al., 2004, Eur J Immunol
IL-12/IFN-g Plasmodium berghei XAT CBA/JNCrj rIL-12 + anti-IFN-g no yes N.I. N.I. Increased and no clearance N.I. Yoshimoto et al., 1998, J Infect Dis
IL-12/IFN-g Plasmodium chabaudi chabaudi AS A/J rIL-12 + anti-IFN-g yes 50% N.I. N.I. Delayed peak (days) and increased recrudescences N.I. Stevenson et al., 1995, J Immunol
IL-12/IFN-g/TNF-a Plasmodium chabaudi chabaudi AS A/J rIL-12 + anti-IFN-g + anti-TNF-a yes yes N.I. N.I. Delayed peak (days) and increased recrudescences N.I. Stevenson et al., 1995, J Immunol
IL-12/NK cells Plasmodium chabaudi chabaudi AS A/J rIL-12 + anti-asialo GM1 yes yes N.I. N.I. Increased peak N.I. Mohan et al., 1997, J Immunol
IL-12/NOS2 Plasmodium chabaudi chabaudi AS A/J rIL-12 + NOS2 inhibitor yes 54-67% N.I. N.I. Similar N.I. Stevenson et al., 1995, J Immunol
IL-12/TNF-a Plasmodium chabaudi chabaudi AS A/J rIL-12 + anti-TNF-a yes yes N.I. N.I. Similar N.I. Stevenson et al., 1995, J Immunol
IL-12p40 Plasmodium berghei ANKA C57BL/6 IL-12p40 -/- yes ~85% (at the end of observation day 20) CM (100%) CM (~85% at the end of observation day 20) N.I. N.I. Berghout et al., 2013, PLoS Pathog
IL-12p40 Plasmodium berghei NK65 C57BL/6J IL-12 -/- yes N.I. Liver pathology No liverpathology Similar ↓ GPT (ALT) serum levels; no liver injury; similar infiltration of lymphocytes in liver Adachi et al., 2001, J Immunol
IL-12p40 Plasmodium berghei NK65 C57BL/6 anti-IL-12p40 yes yes Liver pathology Liver pathology Similar Prolonged survival (~ 1 week); ↓serum AST and ALT; ↓ liver injury; ↓ in vitro production of IFN-g by spleen and liver cells Yoshimoto et al., 1998, J Immunol
IL-12p40 Plasmodium chabaudi chabaudi AS 129/Sv x C57BL/6J IL-12p40 -/- no no N.I. N.I. Increased first peak and developed a prominent second peak Similar protection during second challenge; first peak (day 7): no NO or IFN-g production by spleen cells, no NO secretion after IFN-g stimulation of spleen cells; second peak (day 15): no NO production by spleen cells, similar NO secretion after IFN-g stimulation of spleen cells;↓ NO and ↑ TGF-b1 production by macrophages after stimulation with pRBCs or rIFN-g; ↓ internalization of pRBCs coated with immune serum antibodies by macrophages Bastos et al., 2002, J Interferon Cytokine Res
IL-12p40 Plasmodium chabaudi chabaudi AS C57BL/6 anti-IL-12p40 no no N.I. N.I. Increased peak and increased recrudescences N.I. Stevenson et al., 1995, J Immunol
IL-12p40 Plasmodium chabaudi chabaudi AS 129/Sv x C57BL/6J IL-12p40 -/- no ♀ no; ♂ 40 % Anemia Anemia Increased peak and increased recrudescences, no parasite clearance 40 days p.i. ↓ hematocrit levels and body weight; similar splenomegaly; ↓ serum IFN-g ; ↓ IFN-g production by splenic NK cells; ↓ NK cell cytotoxicity; ↑ IL-10, similar TNF-a and ↓ IFN-g production by spleen cells 7 days p.i.; similar IL-4 production by spleen cells 21 days p.i.; ↓ serum parasite-specific total Ig, IgM and IgG2a,↑ IgG1 15 and 21 days p.i.; no protection against challenge infection; ↓ IgG2a and IgG3, ↑ IgG1 and similar IgG2b 7 days after challenge infection; KO immune sera or IgG2a depleted WT immune serum did not protect susceptible A/J mice Su et al., 2002, J Immunol
IL-12p40 Plasmodium chabaudi chabaudi AS 129/Sv x C57BL/6J IL-12p40 -/- + rIL-12 no no Anemia Anemia Increased recrudescences, but less than without rIL-12 Similar serum levels of parasite-specific total Ig, IgM and IgG2a, ↓ IgG1; similar protection against challenge infection; similar IgG2a, IgG3, IgG1 and IgG2b 7 days after challenge infection Su et al., 2002, J Immunol
IL-15 Plasmodium chabaudi chabaudi AS C57BL/6 IL-15 -/- no 10% N.I. N.I. Increased and persistent low parasitemia ↓serum IFN-g, TNF-a, IL-12p70 and similar IL-10; ↑ number of apoptotic NK cells 5 days p.i.; ↓ NK cell cytotoxicity and in vitro IFN-g production; ↓ parasite-specific total IgG, IgG1, IgG2a, IgG2b, IgG3 and IgM Ing et al., 2005, Infect Immun
IL-17 Plasmodium berghei ANKA C57BL/6 IL-17-/- (17KO) yes yes CM (80%) CM (80%) Similar Similar neurological symptoms Ishida et al., 2010, Biochem Biophys Res Commun
IL-18 Plasmodium berghei ANKA BALB/c IL-18 -/- yes yes N.I. N.I. N.I. Earlier death (~ 1 week) Singh et al., 2002, J Immunol
IL-18 Plasmodium berghei ANKA BALB/c anti-IL-18 yes yes N.I. N.I. N.I. Earlier death (~ 1 week) Singh et al., 2002, J Immunol
IL-18 Plasmodium berghei ANKA C57BL/6 rIL-18 yes yes N.I. N.I. N.I. Prolonged survival (~ 2 weeks) Singh et al., 2002, J Immunol
IL-18 Plasmodium berghei ANKA BALB/c rIL-18 yes yes N.I. N.I. Delayed onset Prolonged survival (days – weeks: dose-dependent) due to ↑ serum IFN-g production; ↓ liver and spleen pathology Singh et al., 2002, J Immunol
IL-18 Plasmodium berghei NK65 C57BL/6 IL-18 -/- yes yes Liver pathology Liver pathology Similar Similar GPT (ALT) serum levels and liver injury Adachi et al., 2001, J Immunol
IL-18 Plasmodium yoelii 17XNL C57BL/6 IL-18 -/- no no N.I. N.I. Increased N.I. Cramer et al., 2008, Microbes Infect
IL-18 Plasmodium yoelii 265 BALB/c rIL-18 20% 0-20% (dose-dependent) N.I. N.I. Delayed onset and decreased peak (dose-dependent) Dose-dependant survival due to ↑ serum IFN-g production; ↓ liver and spleen pathology Singh et al., 2002, J Immunol
IL-18/CTLA-4 Plasmodium berghei ANKA C57BL/6 IL-18 -/- + anti-CTLA-4 yes yes Moderate liver pathology Moderate liver pathology N.I. ↓ serum AST compared to anti-CTLA-4-treated WT and similar to untreated WT; similar serum ALT compared to anti-CTLA-4-treated WT mice and ↑ compared to untreated WT; ↑ CD4+ T cells in liver compared to untreated WT and untreated IL-18 -/- mice (similar compared to anti-CTLA-4-treated WT mice) Jacobs et al., 2004, Eur J Immunol
IL-1a Plasmodium berghei K173 C57BL/6J rIL-1a yes N.I. CM (100%) CM (22%) Delayed ↓ CM incidence only when administered for 6 consecutive days and dose-dependent; no cerebral hemorrhages; no decrease in body temperature; no differences in erythropoiesis Curfs et al., 1990, J Exp Med
IL-1a Plasmodium berghei K173 C57BL/6J-nu rIL-1a yes N.I. N.I. N.I. Similar N.I. Curfs et al., 1990, J Exp Med
IL-1a/IFN-g Plasmodium berghei K173 C57BL/6J rIL-1a + anti-IFN-g yes N.I. CM No CM Similar N.I. Curfs et al., 1990, J Exp Med
IL-1b Plasmodium berghei K173 C57BL/6J rIL-1b yes N.I. CM No CM Delayed N.I. Curfs et al., 1990, J Exp Med
IL-1R Plasmodium berghei ANKA N.I. IL-1R -/- yes yes CM (100%) CM (100%) N.I. N.I. Reimer et al., 2010, Eur J Immunol
IL-1R Plasmodium yoelii 17XNL C57BL/6 IL-1R -/- no no N.I. N.I. Increased N.I. Cramer et al., 2008, Microbes Infect
IL-2 Plasmodium berghei ANKA 129 x C57BL/6 IL-2 -/- yes yes CM (70%) No CM N.I. N.I. Yañez et al., 1996, J Immunol
IL-2 Plasmodium chabaudi adami 556KA 129/Ola x C57BL/6 (WT = 129/Ola) IL-2 -/- no no N.I. N.I. Delayed clearance N.I. Van der heyde et al., 1997, Exp Parasitol
IL-2 Plasmodium chabaudi chabaudi AS 129 x C57BL/6 IL-2 -/- no 25% N.I. N.I. Delayed peak and delayed clearance ↑ Mac-1+, ↓ CD3+ (especially CD8+ and gd+) and B cells in the spleen Seixas et al., 2002, Parasite Immunol
IL-2 Plasmodium yoelii 17XL DBA/2 rIL-2 no yes None CM (100%) Similar Splenocytes 3 days p.i.: ↓ IFN-g , ↑ NO and IL-10; splenocytes 6 days p.i.: similar IFN-g and IL-10, ↑ NO; cerebral accumulation of pRBCs and CD25+ ICAM-1+ T cells (mostly gd T cells) Haque et al., 2001, Am J Pathol
IL-2 Plasmodium yoelii 17XNL BALB/c rIL-2 no 70% N.I. N.I. Decreased peak Induction of IL-2, IFN-g, IL-6 and IL-10 mRNA expression in splenic cells; ↑ CD3 or ConA-induced lymphocyte proliferation Lucas et al., 1996, C R Acad Sci III
IL-2 Plasmodium yoelii 17XNL 129/Ola x C57BL/6 (WT = 129/Ola) IL-2 -/- no no N.I. N.I. Delayed clearance N.I. Van der heyde et al., 1997, Exp Parasitol
IL-2/B cells Plasmodium chabaudi chabaudi AS 129 x C57BL/6 IL-2 -/- x m-MT no yes N.I. N.I. Delayed peak ↑ % of Mac-1+ and CD4+ cells and ↓ % of CD8, gd and B cells in the spleen Seixas et al., 2002, Parasite Immunol

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