|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
ASC |
Plasmodium berghei ANKA |
N.I. |
ASC -/- |
yes |
yes |
CM (100%) |
CM (100%) |
N.I. |
N.I. |
Reimer et al., 2010, Eur J Immunol |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
C3aR |
Plasmodium berghei ANKA |
129/SvJ x C57BL/6 |
C3aR -/- |
yes |
yes |
CM |
CM |
N.I. |
N.I. |
Ramos et al., 2011, J Immunol |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
CD11c/CD18 (CR4) |
Plasmodium berghei ANKA |
C57BL/6 |
CR4 -/- |
yes |
yes |
CM (100%) |
CM (~80%) |
Similar |
N.I. |
Ramos et al., 2012, Parasite Immunol |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
CD14 |
Plasmodium berghei ANKA |
C57BL/6 |
CD14 -/- |
yes |
yes |
CM (100%) |
CM (100%) |
Similar |
N.I. |
Togbe et al., 2007, Am J Pathol |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
CD4 |
Plasmodium berghei ANKA |
C57BL/6 |
CD4 -/- |
yes |
yes |
CM (53%) |
No CM |
N.I. |
N.I. |
Boubou et al., 1999, Int Immunol |
Link |
|
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 |
Link |
|
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 |
Link |
|
CD4 |
Plasmodium berghei ANKA |
C57BL/6J |
anti-CD4 (early treatment) |
yes |
yes |
CM (94%) |
CM (50%) |
Similar |
N.I. |
Hermsen et al., 1997, Parasitology |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
CD4 |
Plasmodium berghei K173 |
C57BL/6J |
anti-CD4 (early treatment) |
yes |
yes |
CM (91%) |
CM (5%) |
Similar |
N.I. |
Hermsen et al., 1997, Parasitology |
Link |
|
CD4 |
Plasmodium berghei K173 |
C57BL/10 |
anti-CD4 (early treatment) |
yes |
yes |
CM (75%) |
CM (25%) |
Similar |
N.I. |
Hermsen et al., 1997, Parasitology |
Link |
|
CD4 |
Plasmodium berghei NK65 |
CBA/JNCrj |
anti-CD4 |
yes |
yes |
N.I. |
N.I. |
Similar |
No prolonged survival |
Waki et al., 1992, Immunology |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |
|
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 |
Link |