Mouse treatment

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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.

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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
a4 integrin chain Plasmodium berghei ANKA CBA/Ca anti-a4 integrin yes yes CM (100%) CM (100%) Similar N.I. Falanga et al., 1991, Eur J Immunol
ab T cell Plasmodium berghei ANKA 129/Sv x C57BL/6 ab TCR -/- yes yes CM (53%) No CM Similar N.I. Boubou et al., 1999, Int Immunol
ab T cell Plasmodium berghei ANKA C57BL/6J b TCR -/- yes yes CM No CM N.I. N.I. Reimer et al., 2010, Eur J Immunol
ab T cell Plasmodium berghei ANKA C57BL/6J b TCR -/- + adoptive transfer of a mixture of CD4+ and CD8+ T cells from WT or Nlrp3-/- mice yes yes CM CM (33%) N.I. N.I. Reimer et al., 2010, Eur J Immunol
ABCA1 Plasmodium berghei ANKA DBA/1 ABCA1 -/- yes yes CM (88%) No CM Similar Prolonged survival (1-2 weeks); ↓ plasma TNF-a; ↓ ICAM-1, VCAM-1, LFA-1, CD41/CD61 and TNF-a protein in the brain; similar CD40 protein in the brain; ↓ leukocyte sequestration in brain vessels; ↓ plasma HDL cholesterol; ↓ MP production due to ↓ response to vesiculation agonists; ↓ procoagulant activity by MP Combes et al., 2005, Am J Pathol
Apo-AI Plasmodium berghei ANKA 129/Ola x C57BL/6J Apo-AI -/- yes yes CM (85%) CM (100%) N.I. ↓ plasma HDL cholesterol Combes et al., 2005, Am J Pathol
Arachidonic acid Plasmodium berghei K173 C57BL/6J fish oil (structural analog of arachidonic acid) yes yes CM (95%) CM (31.5%) Decreased N.I. Blok et al., 1992, J Infect Dis
ASC Plasmodium berghei ANKA N.I. ASC -/- yes yes CM (100%) CM (100%) N.I. N.I. Reimer et al., 2010, Eur J Immunol
B cells Plasmodium berghei ANKA C57BL/6 x 129 µ-chain -/- (µ-MT ) yes yes CM (100%) CM (75%) N.I. N.I. Yañez et al., 1996, J Immunol
B cells Plasmodium berghei ANKA C57BL/6 x 129 JH-gene segment -/- (JHD -/-) yes yes CM (89%) CM (26%) N.I. N.I. Yañez et al., 1996, J Immunol
B cells Plasmodium chabaudi chabaudi AS C57BL/6 m-BCR -/- (m-MT) no no N.I. N.I. Developed a chronic low parasitemia (1-10%) Similar precursor frequencies of CD4+ T cells able to proliferate in response to malarial antigens; CD4+ T cells were still of a predominant IFN-g (Th1) phenotype at the later stages of infection (no switch toward a IL-4 (Th2) phenotype); parasite clearance after adoptive transfer (in the chronic phase) of B cells which restores the Th2 response Langhorne et al., 1998, Proc Natl Acad Sci U S A
B cells Plasmodium chabaudi chabaudi AS C57BL/6 m-BCR -/- (m-MT) no 25% N.I. N.I. Developed a chronic low parasitemia (1-10%) ↑ gd T cells in the spleen 35 days p.i.; no ↓ in the % of splenic IFN-g-producing gd T cells 3-4 weeks p.i.; ↓ % of splenic IL-4-producing gd T cells Seixas et al., 1999, J Immunol
B cells Plasmodium chabaudi chabaudi AS C57BL/6 m-BCR -/- (m-MT) no 30-40 % N.I. N.I. No parasite clearance ↑ gd T cells and similar Mac-1+ cells in spleen Seixas et al., 2002, Parasite Immunol
B cells Plasmodium chabaudi chabaudi AS NIH anti-m-chain from birth (no B cells) no no N.I. N.I. Developed a chronic low parasitemia (~1%) No parasite-specific antibodies; no serum antibody of any Ig isotype detected; reconstitution with B cells restored parasite clearance Taylor-Robinson et al., 1996, Infect Immun
B cells Plasmodium chabaudi chabaudi AS C57BL/6 m-BCR -/- (m-MT) no ♂ 71 %; ♀ 37 % N.I. N.I. Increased recrudescences and no parasite clearance in 40 days No resistance to a secondary infection; parasite clearance after adoptive transfer (in the chronic phase) of B cells (full clearance) or immune serum (partial clearance) from immune donors; ↑ gd T cells and similar Mac-1+ cells in spleen; gd T cells returned to normal levels after parasite clearance (adoptive transfer of B cells, chloroquine treatment) Von der Weid et al., 1996, J Immunol
B cells Plasmodium yoelii 17XNL BALB/cAnN anti-m-chain from birth (no B cells) 10% yes N.I. N.I. Increased without clearance N.I. Weinbaum et al., 1976, J Immunol
B cells/gd T cells Plasmodium chabaudi chabaudi AS 129/Sv x C57BL/6 m-MT x d -/- TCR no 25% N.I. N.I. Developed a high persistent parasitemia (10-30%) N.I. Seixas et al., 1999, J Immunol
B cells/gd T cells Plasmodium chabaudi chabaudi AS C57BL/6 m-BCR -/- (m-MT) + anti-gd TCR no N.I. N.I. N.I. Increased peak and developed a high, persistent parasitemia (around 20%) Anti-gd antibody caused slightly higher peak and significantly higher persistent parasitemia compared to control treated m-MT mice Seixas et al., 1999, J Immunol
B cells/IFN-g Plasmodium chabaudi adami 556KA JHD-/- (no B cells) JHD-/- (no B cells) + anti-IFN-g no no N.I. N.I. Persistent high parasitemia N.I. Van der heyde et al., 1997, Exp Parasitol
B/C2 Plasmodium chabaudi chabaudi AS 129/Sv H2-Bf/C2 -/- no no N.I. N.I. Slightly delayed and slightly increased peak ↑serum IFN-g 6, 8 and 9 days p.i. Taylor et al., 2001, Infect Immun
b2 integrin (CD18) Plasmodium berghei ANKA C57BL/6J CD18 -/- N.I. N.I. N.I. N.I. N.I. ↑ LN cellularity; similar splenomegaly; no significant apoptosis in white pulp (spleen) and LN Piguet et al. 2001, Dev Immunol
Bcl-2 Plasmodium berghei ANKA C57BL/6 over-expression of bcl-2 in myeloid cells (hMRP8-Bcl-2 mice) yes yes CM (100%) CM (100%) N.I. Similar number of TUNEL-positive cells in the brain Helmers et al., 2008, Am J Trop Med Hyg
C1q Plasmodium chabaudi chabaudi AS 129/Sv C1qa -/- no no N.I. N.I. Slightly delayed and slightly increased peak ↑ parasitemia during secondary infection; similar Ab responses during primary infection; ↓ parasite-spec IgG2a 100 days p.i.; ↑ parasite-spec IgM and IgG2a after second challenge (120 days p.i.); ↑serum IFN-g 5, 7 and 9 days p.i.; no difference in IFN-g and IL-4 producing CD4+ T cells or precursor frequenties Taylor et al., 2001, Infect Immun
C3aR Plasmodium berghei ANKA 129/SvJ x C57BL/6 C3aR -/- yes yes CM CM N.I. N.I. Ramos et al., 2011, J Immunol
C3aR/C5aR Plasmodium berghei ANKA 129 x C57BL/6 C3aR -/- + C5aR -/- yes yes CM CM N.I. N.I. Ramos et al., 2011, J Immunol
C5 Plasmodium berghei ANKA C57BL/6 C5 -/- yes yes CM (100%) CM (<10%) N.I. ↓ serum TNF and IL-6; ↓ brain CD8+ T cells Ramos et al., 2011, J Immunol
C5a Plasmodium berghei ANKA B10.D2/nSnJ anti-C5a yes yes CM (100%) CM (25%) N.I. N.I. Patel et al., 2008, J Exp Med
C5a Plasmodium berghei ANKA C57BL/6 12.5% DNA from A/J mice (including the C5 mutant gene) (= BcA76) yes yes CM (100%) CM (90%) Similar Slightly reduced CM incidence and survival Patel et al., 2008, J Exp Med
C5a Plasmodium berghei ANKA A/J 12.5% DNA from C57BL/6 mice (including the C5 WT gene) (= AcB55) yes yes Delayed CM CM (100%) Similar Accelerated development of CM Patel et al., 2008, J Exp Med
C5aR Plasmodium berghei ANKA B10.D2/nSnJ anti-C5aR yes yes CM (100%) CM (25%) N.I. N.I. Patel et al., 2008, J Exp Med
C5aR Plasmodium berghei ANKA 129 x C57BL/6 C5aR -/- yes yes CM (~90%) CM (~80%) N.I. N.I. Ramos et al., 2011, J Immunol
C9 Plasmodium berghei ANKA C57BL/6 anti-C9 yes yes CM (100%) CM (~80%) N.I. Delayed onset of CM Ramos et al., 2011, J Immunol
Caspase-1 Plasmodium berghei ANKA C57BL/6 x 129/S2SvPas Casp1 -/- yes yes CM (55%) CM (60%) Similar Similar serum IL-1b 10 days p.i.; similar mRNA expression of TNF-a, IL-6, MCP-1 and MIP-1 in the brain 10 days p.i. Labbé et al., 2010, J Immunol
Caspase-1 Plasmodium berghei ANKA N.I. Caspase-1 -/- yes yes CM (100%) CM (100%) N.I. N.I. Reimer et al., 2010, Eur J Immunol
Caspase-1 Plasmodium chabaudi AS C57BL/6 x 129/S2SvPas Casp1 -/- no no N.I. N.I. Similar Similar serum IFN-g, TNF-a, IL-10; similar serum IgG1 and IgG2a 21 days p.i.; ↓ serum IL-18 6-7 days p.i.; similar anemia and weight loss; similar production of IFN-g, IL-10 and IL-1b by splenocytes after stimulation with pRBCs Labbé et al., 2010, J Immunol
Caspase-12 Plasmodium berghei ANKA C57BL/6 Casp12 -/- yes yes CM (55%) CM (90%) Similar ↑ serum IL-1b 10 days p.i.; ↑ mRNA expression of TNF-a, IL-6, MCP-1 and MIP-1 in the brain 10 days p.i. Labbé et al., 2010, J Immunol
Caspase-12 Plasmodium chabaudi AS C57BL/6 Casp12 -/- no no N.I. N.I. Decreased peak and decreased recrudescences ↓ weight loss at the peak of infection; ↑ serum IFN-g 5-7 days p.i., ↑ serum TNF-a and IL-10 6 days p.i. and ↑ serum IL-18 7 days p.i.; similar serum IgG1 and ↑ IgG2a 21 days p.i.; ↑ production of IFN-g, TNF-a, IL-10 and IL-1b by splenocytes after stimulation with pRBCs for 48h; similar liverpathology 10 days p.i. (serum ALT, liver necrosis and inflammation); similar pro-IL-1b mRNA expression in the spleen 6 days p.i.; ↑ caspase-1 activation in BMDMs after stimulation with pRBCs; similar IkBa and ↑Bcl-xl, cox-2 protein in the spleen 7 days p.i.; Labbé et al., 2010, J Immunol
Caspase-12/caspase-1 Plasmodium chabaudi AS C57BL/6 Casp12 -/- + selective caspase-1 inhibitor (YVAD) No No N.I. N.I. Similar Similar serum IgG1 and ↑ IgG2a 21 days p.i. (similar compared to untreated infected casp12 -/- mice) Labbé et al., 2010, J Immunol
Caspase-12/IFN-g Plasmodium chabaudi AS C57BL/6 Casp12 -/- + anti-IFN-g no no N.I. N.I. Similar Similar serum IgG2a 21 days p.i. (↓ compared to untreated infected casp12 -/- mice) Labbé et al., 2010, J Immunol
Caspase-12/IKK Plasmodium chabaudi AS C57BL/6 Casp12 -/- + IKK inhibitor no no N.I. N.I. Similar Similar serum IgG2a 21 days p.i. (↓ compared to untreated infected casp12 -/- mice) Labbé et al., 2010, J Immunol
caspases Plasmodium berghei ANKA C57BL/6 caspase inhibitor (ZVAD-fmk) yes yes CM (100%) CM (100%) N.I. The inhibitor does not cross the BBB, making it difficult to prevent neuronal apoptosis Helmers et al., 2008, Am J Trop Med Hyg
caspases Plasmodium berghei ANKA C57BL/6J caspase inhibitor (ZVAD-fmk) yes yes CM (100%) CM(~65 %) Similar ↓ thrombocytopenia and ↓ microparticles in plasma Piguet et al., 2002, Apoptosis
Catecholamines Plasmodium berghei Pasteur Swiss -44 phenoxybenzamine (alpha-adrenergic receptor antagonist) yes yes N.I. N.I. Similar Protects against pulmonary edema, although significance was not reached Cordeiro et al., 1984, Experiencia
CCR2 Plasmodium berghei ANKA C57BL/6 x 129/Ola CCR2 -/- yes yes CM (70%) CM (100%) Similar ↓ macrophages, CD4+ T cell, PMN and similar CD8+ T cells in the brain; depletion of CD8+ T cells, but not of CD4+ T cells or PMNs, rescued these mice from CM Belnoue et al., 2003, Infect Immun
CCR5 Plasmodium berghei ANKA C57BL/6 x 129/Ola CCR5 -/- yes yes CM (70-80%) CM (20%) Similar Prolonged survival (1-3 weeks); similar anemia; no neurologic symptoms; ↓ leukocyte sequestration in brain; no IFN-g and ↓ TNF-a in serum; ↓ incidence of CM (or ↑ incidence) by adoptive transfer of bone marrow from CCR5 -/- (or WT) into irradiated WT (or CCR5 -/-) mice Belnoue et al., 2003, Blood
CCR5 Plasmodium berghei ANKA C57BL/6 CCR5 -/- yes yes CM (100%) CM (100%) N.I. CM was delayed for 1 day Nitcheu et al., 2003, J Immunol
CD11a/CD18 (LFA-1) Plasmodium berghei ANKA CBA/Ca anti-CD11a yes yes CM (100%) CM (i.v.0%; i.p.30%) Similar Prolonged survival (2-3 weeks: late as well as early treatment, no effect if administered when symptoms were evident); no neurological symptoms; ↑ protection when administered i.v. compared to i.p.; similar mononuclear cell sequestration in the brain (WT: sequestering cells are almost all monocytes or mononuclear phagocytes, only very few T, B cells or neutrophils were observed) Falanga et al., 1991, Eur J Immunol
CD11a/CD18 (LFA-1) Plasmodium berghei ANKA CBA/Ca anti-CD11a yes 70% (at the end of observation week 4) CM (85%) CM (10%) Similar Prolonged survival (2-3 weeks: late as well as early treatment, no effect if administered when symptoms are evident); no neurological symptoms; ↓ serum TNF-a; similar mononuclear cell sequestration in the brain Grau et al., 1991, Eur J Immunol
CD11a/CD18 (LFA-1) Plasmodium berghei ANKA CBA/J anti-CD11a yes yes CM No CM N.I. ↓ platelet sequestration in brain and similar platelet sequestration in lung Grau et al., 1993, Eur Cytokine Netw
CD11a/CD18 (LFA-1) Plasmodium berghei ANKA C57BL/6 LFA1 -/- yes yes CM (100%) CM (20%) Similar N.I. Ramos et al., 2012, Parasite Immunol
CD11a/CD18 (LFA-1) Plasmodium berghei ANKA CBA/Ca anti-CD11a yes yes CM (85-90%) N.I. Similar Prolonged survival (2-3 weeks: late as well as early treatment); no neurological symptoms; no vascular permeability in brain and ↓vascular permeability in lungs; ↓ mononuclear cell sequestration in brain and lungs; ↓ (brain) and similar (lungs) platelet accumulation; similar microhemorrhages in the brain; ↓ myeloperoxidase activity (neutrophil enzyme) in lungs; similar liver pathology; ↓injected aggregated albumin localization in brain and lungs Senaldi et al., 1994, Infect Immun
CD11b/CD18 (Mac-1, CR3) Plasmodium berghei ANKA CBA/Ca anti-CD11b yes yes CM (100%) CM (100%) Similar N.I. Falanga et al., 1991, Eur J Immunol
CD11b/CD18 (Mac-1, CR3) Plasmodium berghei ANKA CBA/Ca anti-CD11b yes yes CM (85%) CM (100%) Similar N.I. Grau et al., 1991, Eur J Immunol
CD11b/CD18 (Mac-1, CR3) Plasmodium berghei ANKA CBA/J anti-CD11b yes yes CM CM N.I. Similar platelet sequestration in brain and lung Grau et al., 1993, Eur Cytokine Netw
CD11b/CD18 (Mac-1, CR3) Plasmodium berghei ANKA C57BL/6 CR3 -/- yes yes CM (~90%) CM (~80%) Increased N.I. Ramos et al., 2012, Parasite Immunol
CD11c/CD18 (CR4) Plasmodium berghei ANKA C57BL/6 CR4 -/- yes yes CM (100%) CM (~80%) Similar N.I. Ramos et al., 2012, Parasite Immunol
CD11d/CD18 Plasmodium berghei ANKA 129/Sv x C57BL/6 aD -/- yes yes CM (~75%) CM (~50%) Similar Similar anemia; ↓ serum IL-12p40 Miyazaki et al., 2007, J Immunol
CD134L Plasmodium chabaudi chabaudi AS C57BL/6 anti-CD134L (anti-OX89) no no N.I. N.I. Similar Less severe weight loss and hypothermia; ↓ serum levels (in vivo) and production of IFN-g and TNF-a by splenocytes (in vitro) Franklin et al., 2007, Microbes Infect
CD14 Plasmodium berghei ANKA C57BL/6 anti-CD14 yes no (at the end of observation day 10) CM (80% at the end of observation day 10) No CM (at the end of observation day 10) N.I. N.I. Srivastava et al., 2010, PLoS ONE
CD14 Plasmodium berghei ANKA C57BL/6 CD14 -/- yes yes CM (100%) CM (100%) Similar N.I. Togbe et al., 2007, Am J Pathol
CD14 Plasmodium chabaudi chabaudi AS C57BL/6 CD14 -/- no no N.I. N.I. Similar Similar hypothermia and weight loss during peak parasitemia; similar TNF-a, IFN-g and MCP-1 production by splenocytes 8 days p.i.; similar serum levels of TNF-a, IFN-g and MCP-1 8 days p.i. Franklin et al., 2007, Microbes Infect
CD1d-restricted NKT cells Plasmodium berghei NK65 129/Sv x C57BL/6 CD1d -/- yes yes Liver pathology Liver pathology N.I. Similar serum GPT (ALT) and liver injury Adachi et al., 2001, J Immunol
CD1d-restricted NKT cells Plasmodium berghei NK65 129/Sv x C57BL/6 CD1d -/- yes yes Liver pathology Liver pathology N.I. Similar liver injury; similar ↑ in hepatic CD3+NK1.1+ and CD3+DX5+ cells; similar cytotoxicity by hepatic lymphocytes (↑ cytotoxicity by DX5+ enriched cells) against hepatocytes was abrogated after depletion of DX5+ lymphocytes (= DX5+CD1d-unresctricted NKT cells) Adachi et al., 2004, Int Immunol
CD36 Plasmodium berghei ANKA C57BL/6 x 129/Sv CD36 -/- chimeras yes yes CM (100%) CM (75%) Similar 25 % of CD36 -/- chimeras expressing only CD36 in hematopoietic cells had a prolonged survival (2-3 weeks) without neurological symptoms Cunha-Rodrigues et al., 2007, Malar J
CD36 Plasmodium berghei ANKA C57BL/6 x 129/Sv CD36 -/- yes yes CM (100%) CM (100%) Slightly decreased Similar neurologic symptoms; ↓ schizont sequestration in adipose and lung tissue; no schizont sequestration in brain (similar to WT); ↑ parasite accumulation in spleen (↑ pRBC clearance?); ↑ number of schizonts in peripheral blood Franke-Fayard et al., 2005, Proc Natl Acad Sci U S A
CD36 Plasmodium berghei ANKA C57BL/6 CD36 -/- yes yes ALI, CM (100%) ↓ ALI, CM (100%) Similar ↓ lung pathology: ↓ IgM in bronchoalveolar lavage fluid Lovegrove et al., 2008, PLoS Pathog
CD4 Plasmodium berghei ANKA C57BL/6 anti-CD4 (early treatment) yes yes CM (100%) No CM N.I. No neurological symptoms; prolonged survival Beghdadi et al., 2008, J Exp Med
CD4 Plasmodium berghei ANKA C57BL/6 anti-CD4 (late treatment) yes yes CM (100%) CM (100%) N.I. N.I. Belnoue et al., 2003, Infect Immun
CD4 Plasmodium berghei ANKA 129P2Sv/Ev anti-CD4 (late treatment) yes yes CM (60-100%) No CM N.I. N.I. Belnoue et al., 2008, Parasite Immunol
CD4 Plasmodium berghei ANKA C57BL/6 CD4 -/- yes yes CM (53%) No CM N.I. N.I. Boubou et al., 1999, Int Immunol
CD4 Plasmodium berghei ANKA CBA/Ca, CBA/J CD4+ T cells from mice with CM (LN derived) yes yes CM (100%) CM (100%) N.I. More severe brain hemorrhages and earlier mortality when mice received CD4+ T cells from mice dying of CM than from normal mice Grau et al., 1986, J Immunol
CD4 Plasmodium berghei ANKA CBA/J, CBA/Ca anti-CD4 yes yes CM (79%) No CM N.I. No neurological symptoms; prolonged survival (~ 2 weeks); ↓ serum TNF-a Grau et al., 1987, Science
CD4 Plasmodium berghei ANKA C57BL/6J anti-CD4 (early treatment) yes yes CM (94%) CM (50%) Similar N.I. Hermsen et al., 1997, Parasitology
CD4 Plasmodium berghei ANKA C57BL/6 anti-CD4 (early treatment) yes yes CM (87,5%) No CM N.I. No neurological symptoms; prolonged survival Yañez et al., 1996, J Immunol
CD4 Plasmodium berghei ANKA C57BL/6 anti-CD4 (early treatment) yes yes CM (67%) No CM N.I. No neurological symptoms; prolonged survival (~2 weeks) Yañez et al., 1999, Infect Immun
CD4 Plasmodium berghei ANKA C57BL/6 anti-CD4 (late treatment) yes yes CM (67%) CM (67%) N.I. N.I. Yañez et al., 1999, Infect Immun
CD4 Plasmodium berghei K173 C57BL/10 anti-CD4 (early treatment) yes yes CM (75%) CM (25%) Similar N.I. Hermsen et al., 1997, Parasitology
CD4 Plasmodium berghei K173 C57BL/6J anti-CD4 (late treatment) yes yes CM (91%) CM (0-12%) Similar N.I. Hermsen et al., 1997, Parasitology
CD4 Plasmodium berghei K173 C57BL/6J anti-CD4 (early treatment) yes yes CM (91%) CM (5%) Similar N.I. Hermsen et al., 1997, Parasitology
CD4 Plasmodium berghei NK65 CBA/JNCrj anti-CD4 yes yes N.I. N.I. Similar No prolonged survival Waki et al., 1992, Immunology
CD4 Plasmodium berghei XAT CBA/JNCrj anti-CD4 no yes N.I. N.I. Increased No resistance to P. berghei NK65 challenge infection Waki et al., 1992, Immunology
CD4 Plasmodium chabaudi chabaudi AS C57BL/6 anti-CD4 no no N.I. N.I. No parasite clearance in 28 days Less severe weight loss and hypothermia; ↓ serum levels (in vivo) and production of IFN-g and TNF-a by splenocytes (in vitro); TNF-a serum levels and production by splenocytes remained elevated 4 weeks p.i. Franklin et al., 2007, Microbes Infect
CD4 Plasmodium chabaudi chabaudi AS C57BL/6 anti-CD4 N.I. N.I. N.I. N.I. N.I. No detectable serum IFN-g Meding et al., 1990, Infect Immun
CD4 Plasmodium chabaudi chabaudi AS C57BL/6NCrlBR anti-CD4 no no N.I. N.I. Increased peak and developed a high, persistent parasitemia High, persistent parasitemia coincided with the high level of reticulocytosis Podoba et al., 1991, Infect Immun
CD4 Plasmodium chabaudi chabaudi AS C57BL/6 anti-CD4 no no N.I. N.I. Increased peak and developed a high, persistent parasitemia Similar parasite-specific IgM early during infection and no IgG; high, persistent parasitemia coincided with the high level of reticulocytosis Süss et al., 1988, Infect Immun
CD4 Plasmodium yoelii 17XNL C57BL/6 anti-CD4 no yes (100%) N.I. N.I. N.I. Additional therapeutic blockade of PD-L1 and LAG-3 did not improve parasite clearance Butler et al., 2012, Nat Immunol
CD4 Plasmodium yoelii 17XNL CBA/CaJ anti-CD4 no yes N.I. N.I. No parasite clearance N.I. Vinetz et al., 1990, J Immunol
CD4+CD25+Foxp3+ Treg cells Plasmodium berghei ANKA C57BL/6 anti-CD25 (day -1) yes yes CM (90%) CM (20%) Reduced on days 5-7 similar results as with anti-CD25 treatment 1 day before infection (see above), thus the protective effect is probably mediated by natural Treg cells and not by inducible Treg cells (although the latter might contribute as well) Amante et al., 2007, Am J Pathol
CD4+CD25+Foxp3+ Treg cells Plasmodium berghei ANKA C57BL/6 anti-CD25 (day -14) yes yes CM (100%) No CM Reduced on day 5 Prolonged survival (2 weeks) (possible effect of inducible Treg cells??); no neurological symptoms; parasite burden is much higher than estimated by blood smears due to accumulation of parasites in peripheral tissue and vasculature; parasite burden greatly (~10-fold) decreased by anti-CD25; Brain: ↓ pRBC accumulation; similar VCAM-1 and ICAM-1; ↓ CD8+ T cells, ↑ number of macrophages and similar CD4+ T, B, NK, NKT cells, PMN, DC and microglia; similar CD69+CD4+ cells; ↓ CD69+CD8+ T cells; Spleen:↑ CD69+CD4+ and CD69+CD8+ T cells; ↑ IFN-g+ CD4+ and similar IFN-g+CD8+ cells (day 5); similar IFN-g and IL-10 mRNA (day 5); Lymph nodes: CD69+CD4+ and CD69+CD8+ T cells; Blood: ↓ CD69+CD4+ cells; ↓ CD69+CD8+ T cells (no difference between CD69+CD25+ and CD69+CD25- T cells → no depletion of activated CD25+CD4+ or CD25+ CD8+ T cells); ↑ MCP-1, ↓ IL-10 and similar TNF-a and IL-6 (day 5) Amante et al., 2007, Am J Pathol
CD4+CD25+Foxp3+ Treg cells Plasmodium berghei ANKA C57BL/6 anti-CD25 (day 4) yes yes CM (80 %) CM (20%) Similar Therapeutic potential of anti-CD25 treatment was lost when initiated after the onset of neurological symptoms Amante et al., 2007, Am J Pathol
CD4+CD25+Foxp3+ Treg cells Plasmodium berghei ANKA BALB/c anti-CD25 (day -2 and -6h) yes yes No CM CM (20%) Similar ↑ splenic CD4+ T cell proliferation and IL-2 production; ↑ parasite-specific T cell proliferation; similar IL-4 and ↑ IFN-g production by splenic T cells; when challenged with a secondary infection, parasitemia was decreased and mortality by CM increased (up to 80 %) Nie et al., 2007, Infect Immun
CD4+CD25+Foxp3+ Treg cells Plasmodium berghei ANKA C57BL/6 anti-CD25 (day -14) yes yes CM (100%) CM (10%) Reduced total parasite burden Prolonged survival (2 weeks); no neurological symptoms Randall et al., 2008, Infect Immun
CD4+CD25+Foxp3+ Treg cells Plasmodium berghei ANKA CBA anti-CD25 (day -14) yes yes CM (100%) No CM Reduced total parasite burden Prolonged survival (2 weeks); no neurological symptoms Randall et al., 2008, Infect Immun
CD4+CD25+Foxp3+ Treg cells Plasmodium berghei ANKA C57BL/6 anti-CD25 (day -30) yes yes CM (80%) CM (70%) Similar 50% Foxp3+CD4+ cells on day 0 remain Vigário et al., 2007, Int J Parasitology
CD4+CD25+Foxp3+ Treg cells Plasmodium berghei ANKA C57BL/6 anti-CD25 (day - 1 and day 1) yes yes CM (80%) No CM Increased on day 7 Inactivation of both regulatory and effector T cells Vigário et al., 2007, Int J Parasitology
CD4+CD25+Foxp3+ Treg cells Plasmodium chabaudi adami DK BALB/c anti-CD25 (day -1 and +1) no no N.I. N.I. Similar ↑ CD4+FOXP3-CD69+, ↓ CD4+FOXP3-CD25+ and similar CD4-CD69+ lymphocytes in spleen; ↑ parasite-specific IL-2 and similar IFN-g response by CD4+ T cells (in vitro); ↑ IFN-g and similar IL-2 response by CD4+ T cells after stimulation with anti-CD3 (in vitro); similar TNF-a, IFN-g and ↑ IL-10 production by unstimulated CD90- (Thy-1-) splenocytes and ↑ IFN-g prodyction by unstimulated CD4+ cells (in vitro); ↑ anemia Cambos et al., 2008, Int J Parasitol
CD4+CD25+Foxp3+ Treg cells Plasmodium chabaudi adami DS BALB/c anti-CD25 (day -1 and +1) yes yes N.I. N.I. Increased on day 7 Earlier death (1 day); ↑ morbidity; ↓ CD4+FOXP3-CD25+ and similar CD4+FOXP3-CD69+ and CD4-CD69+ lymphocytes in spleen; ↑ parasite-specific IFN-g and similar IL-2 response by CD4+ T cells (in vitro); ↑ IFN-g and similar IL-2 response by CD4+ T cells after stimulation with anti-CD3 (in vitro); ↑ TNF-a, IFN-g and IL-10 production by unstimulated CD90- (Thy-1-) splenocytes and ↑ IFN-g production by unstimulated CD4+ cells (in vitro) ; ↑ anemia Cambos et al., 2008, Int J Parasitol
CD4+CD25+Foxp3+ Treg cells Plasmodium yoelii 17XL BALB/c anti-CD25 (day -3, -1 and 5) yes no N.I. N.I. Developed 2 waves of parasitemia and cleared infection ↑ proliferative response of splenocytes after stimulation with pRBC (in vitro) Hisaeda et al., 2004, Nat Med
CD4+CD25+Foxp3+ Treg cells Plasmodium yoelii 17XNL BALB/c anti-CD25 (day -3, -1 and 5) no no N.I. N.I. Similar N.I. Hisaeda et al., 2004, Nat Med
CD4+CD25+T cells Plasmodium berghei NK65 BALB/c anti-CD25 (day -3, -1 and 5) yes yes N.I. N.I. Delayed (1 day) N.I. Long et al., 2003, Int J Parasitol

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