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
T cells Plasmodium yoelii 17XNL BALB/c-nu/+ Nude mice (nu/nu): no thymus thus no mature T cells no yes N.I. N.I. N.I. ↓ IFN-g and similar IL-4 and TNF-a protein levels in the spleen 24h p.i.; ↑ parasite inoculum was necessary to induce IFN-g production in spleen De Souza et al., 1997, Infect Immun
T cells Plasmodium yoelii 17XNL BALB/c-nu/nu Adoptive transfer of immune CD8+ splenocytes yes yes N.I. N.I. Similar N.I. Vinetz et al., 1990, J Immunol
T cells Plasmodium yoelii 17XNL C57BL/10SnJ Nude mice (nu/nu): no thymus thus no mature T cells no yes N.I. N.I. No parasite clearance N.I. Vinetz et al., 1990, J Immunol
T cells Plasmodium yoelii 17XNL C57BL/10SnJ-nu/nu Adoptive transfer of unfractionated immune splenocytes yes no N.I. N.I. Spontaneous parasite clearance N.I. Vinetz et al., 1990, J Immunol
T cells Plasmodium yoelii 17XNL C57BL/10SnJ-nu/nu Adoptive transfer of unfractionated immune splenocytes + anti-CD8 yes no N.I. N.I. Spontaneous parasite clearance N.I. Vinetz et al., 1990, J Immunol
T cells Plasmodium yoelii 17XNL C57BL/10SnJ-nu/nu Adoptive transfer of unfractionated immune splenocytes + anti-CD4 yes yes N.I. N.I. Similar N.I. Vinetz et al., 1990, J Immunol
T cells Plasmodium yoelii 17XNL BALB/c Nude mice (nu/nu): no thymus thus no mature T cells no yes N.I. N.I. Increased without clearance N.I. Vinetz et al., 1990, J Immunol
T cells Plasmodium yoelii 17XNL BALB/c-nu/nu Adoptive transfer of immune CD4+ splenocytes yes no N.I. N.I. Spontaneous parasite clearance N.I. Vinetz et al., 1990, J Immunol
T cells Plasmodium yoelii 17XNL BALB/cAnN Nude mice (nu/nu): no thymus thus no mature T cells no yes N.I. N.I. Increased without clearance Thymus grafting from birth protected nude mice from a lethal infection; ↑ IgG1, IgG2 and similar IgM levels before and after infection Weinbaum et al., 1976, J Immunol
T cells/CD8 Plasmodium berghei K173 C57BL/6J Thymectomy + anti-CD8 yes yes CM (90%) CM (14%) Similar N.I. Hermsen et al., 1997, Parasitology
T cells/CD8 Plasmodium berghei K173 C57BL/10 Thymectomy + anti-CD8 yes yes CM (100%) No CM Similar N.I. Hermsen et al., 1997, Parasitology
T cells/CD8 Plasmodium chabaudi chabaudi AS NIH Thymectomy + anti-CD8 no no N.I. N.I. Similar N.I. Taylor-Robinson et al., 1993, Science
Taurine Plasmodium chabaudi (N.I.) 129/SvJ x C57BL/6 Taut -/- 10% yes Anemia Multiple organ dysfunction Increased peak All mice died between day 8 and 13 p.i. of MOD (brain, liver, lung and kidney pathology); ↓ circulating taurine levels; similar AST, ALT, bile acid and bilirubin; ↑ plasma ammonia levels; ↑ serum TNF-a and IL-1b; liver: necrotic areas and inflammation; hypertrophic Kuppfer cells with more Hz; no reduction in particle trapping capacity; ↑ IL-1b, TNF-a, IL-6, iNOS, NF-KB, VDR and similar CYP3A11, SULT2B1, UGT1A1, MRP4, Actb mRNA expression Delic et al., 2010, Infect Immun
Testosterone Plasmodium chabaudi chabaudi AS C57BL/6 testosterone ♀24% ♀ yes N.I. N.I. Increased peak Similar reticulocytosis and anemia Wunderlich et al., 2005, Microbes Infect
TGF-b Plasmodium berghei NK65 BALB/c rTGF-b yes yes N.I. N.I. Delayed onset Dose-dependent delay of mortality (2-3 weeks); ↓ serum TNF-a and IL-4; ↑serum IFN-g and IL-10 Omer et al., 1998, J Exp Med
TGF-b Plasmodium berghei NK65 BALB/c anti-TGF-b yes yes N.I. N.I. Earlier onset Earlier death (~ 1 week); ↑ serum TNF-a and similar IFN-g, IL-4 and IL-10 Omer et al., 1998, J Exp Med
TGF-b Plasmodium chabaudi chabaudi A/J BALB/c anti-TGF-b no yes N.I. N.I. No decline N.I. Omer et al., 1998, J Exp Med
TGF-b Plasmodium chabaudi chabaudi AS BALB/c Cr Slc anti-TGF-b yes 20% N.I. N.I. Slightly lower peak and spontaneous decline ↑ serum IFN-g (day 7) and NO (day 10) Tsutsui et al., 1999, Infect Immun
TGF-b Plasmodium chabaudi chabaudi AS C57BL/10 Sn Slc rTGF-b no yes N.I. N.I. No decline and increased ↓ serum IFN-g (day 7) and NO (day 10); abrogated increase of Ly6A/E on CD4+ T cells and abrogated increase of MHC-II on CD11b+ cells in spleen Tsutsui et al., 1999, Infect Immun
TGF-b Plasmodium yoelii 17XL C57BL/6 anti-TGF-b yes yes N.I. N.I. Similar ↑ plasma IL-10 and similar plasma IFN-g and TNF-a Omer et al., 2003, J Immunol
TGF-b Plasmodium yoelii 17XNL BALB/c anti-TGF-b no no N.I. N.I. Similar No effect Omer et al., 1998, J Exp Med
TGF-b/IL-10R Plasmodium yoelii 17XL C57BL/6 anti-TGF-b + anti-IL-10R yes 60% (at the end of observation day 34) N.I. N.I. Complete parasite clearance ↑ plasma TNF-a and slightly ↑ plasma IFN-g Omer et al., 2003, J Immunol
TGF-b1 Plasmodium berghei (N.I.) BALB/c rTGF-b1 (oral) yes yes N.I. N.I. Similar Similar mortality Namangale et al., 2009, Jpn J Vet Res
TIRAP Plasmodium berghei ANKA C57BL/6 TIRAP -/- yes yes CM (100%) CM (100%) Similar N.I. Togbe et al., 2007, Am J Pathol
Tissue PA (tPA) Plasmodium berghei ANKA C57BL/6 x 129/Sv tPA -/- yes yes CM CM N.I. N.I. Piguet et al., 2000, Infect Immun
TLR1 Plasmodium berghei ANKA C57BL/6 TLR1 -/- yes yes CM (100%) CM (100%) Similar N.I. Togbe et al., 2007, Am J Pathol
TLR2 Plasmodium berghei ANKA C57BL/6 TLR2 -/- yes yes CM (90%) CM (45%) Similar Similar serum IL-12p40, IFN-g and TNF-a; ↓ hemozoin clusters in brain vessels Coban et al., 2007, Int Immunol
TLR2 Plasmodium berghei ANKA C57BL/6 TLR2 -/- yes yes CM (100%) CM (100%) Similar Similar thrombocytopenia, neutrophilia and anemia; ↑ lymphopenia Togbe et al., 2007, Am J Pathol
TLR2 Plasmodium chabaudi AS C57BL/6 TLR2 -/- no no N.I. N.I. Similar Similar up-regulation of CD40, CD86 and MHC class II, similar production of TNF-a and IL-12p70, degradation of IkB-a and translocation of NF-kB to the nucleus after incubation of TLR2 -/- DCs with P. berghei or P. chabaudi schizonts; Similar increase of CD40, CD80 and CD86 on splenic DCs isolated from P. berghei-infected mice 6 days p.i. and P. chabaudi-infected mice 7 days p.i. Seixas et al., 2009, Eur J Immunol
TLR2 Plasmodium chabaudi chabaudi AS C57BL/6 TLR2 -/- no no N.I. N.I. Similar Similar hypothermia and weight loss during peak parasitemia; resistant to a secondary infection; similar IgG1 and IgG2a levels; ↓ TNF-a and similar IFN-g and MCP-1 production by splenocytes 8 days p.i.; similar serum levels of TNF-a, IFN-g and MCP-1 8 day Franklin et al., 2007, Microbes Infect
TLR2/4 Plasmodium berghei ANKA C57BL/6 TLR2/4 -/- yes yes CM (100%) CM (100%) Similar N.I. Togbe et al., 2007, Am J Pathol
TLR2/4 Plasmodium berghei NK65 129 x C57BL/6 TLR2/4 -/- yes yes Liver pathology Liver pathology Similar Similar serum IL-12 and liver injury Adachi et al., 2001, J Immunol
TLR2/4 Plasmodium yoelii 17XNL N.I. TLR2/4 -/- no no N.I. N.I. Similar N.I. Cramer et al., 2008, Microbes Infect
TLR2/4/9 Plasmodium berghei ANKA 129/Sv x C57BL/6 TLR2/4/9 -/- yes yes CM (90%) CM (100%) Similar Similar CD8+CD62Llow and ↓ CD4+CD62Llow T cells in brain; similar ICAM-1 and CD31 in brain; similar IL-12p40 and IL-18 in serum Lepenies et al., 2008, Med Microbial Immunol
TLR2/4/9 Plasmodium yoelii 17XNL N.I. TLR2/4/9 -/- no no N.I. N.I. Similar Similar serum IL-12p40 and IL-18 6 days p.i.; ↑ number of CD62Llow+CD4+ and CD69+CD4+ T cells in the spleen 6 days p.i.; no difference in [3H]thymidine uptake upon stimulation of splenocytes with anti-CD3; similar production of IL-12p40, IFN-g and ↑ IL-10 after stimulation of splenocytes isolated 6 days p.i. with anti-CD3 Cramer et al., 2008, Microbes Infect
TLR3 Plasmodium berghei ANKA C57BL/6 TLR3 -/- yes yes CM (100%) CM (100%) Similar N.I. Togbe et al., 2007, Am J Pathol
TLR4 Plasmodium berghei ANKA C57BL/6 TLR4 -/- yes yes CM (90%) CM (85%) Similar N.I. Coban et al., 2007, Int Immunol
TLR4 Plasmodium berghei ANKA C57BL/6 TLR4 -/- yes yes CM (100%) CM (100%) Similar N.I. Togbe et al., 2007, Am J Pathol
TLR4 Plasmodium chabaudi AS C57BL/6 TLR4 -/- no 25% N.I. N.I. Similar Decreased up-regulation of CD40, CD86 and MHC class II, decreased production of TNF-a and IL-12p70, no degradation of IkB-a and no translocation of NF-kB to the nucleus after incubation of TLR4 -/- DCs with P. berghei or P. chabaudi schizonts; Decreased expression of CD40, CD80 and CD86 on splenic DCs isolated from P. berghei-infected mice 6 days p.i. and P. chabaudi-infected mice 7 days p.i. Seixas et al., 2009, Eur J Immunol
TLR4 Plasmodium chabaudi chabaudi AS C57BL/6 TLR4 -/- 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
TLR5 Plasmodium berghei ANKA C57BL/6 TLR5 -/- yes yes CM (85%) CM (100%) Similar N.I. Coban et al., 2007, Int Immunol
TLR6 Plasmodium berghei ANKA C57BL/6 TLR6 -/- yes yes CM (100%) CM (100%) Similar N.I. Togbe et al., 2007, Am J Pathol
TLR6 Plasmodium berghei NK65 129/Sv x C57BL/6 TLR6 -/- yes yes Liver pathology Liver pathology Similar Similar serum IL-12 and liver injury Adachi et al., 2001, J Immunol
TLR6 Plasmodium chabaudi chabaudi AS C57BL/6 TLR6 -/- 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
TLR7 Plasmodium berghei ANKA C57BL/6 TLR7 -/- yes yes CM (100%) CM (100%) Similar N.I. Coban et al., 2007, Int Immunol
TLR7 Plasmodium berghei ANKA C57BL/6 TLR7.tg (SLE-susceptible) yes yes CM (90%) CM (10%) Similar Prolonged survival (days); ↑ splenomegaly; ↓ number of brain microhemorrhages; no kidney inflammation Waisberg et al., 2010, Proc Natl Acad Sci U S A
TLR9 Plasmodium berghei ANKA C57BL/6 TLR9 -/- yes yes CM (85%) CM (54%) Similar Similar serum IL-12p40 and IFN-g; ↓ serum TNF-a; ↓ hemozoin clusters in brain vessels Coban et al., 2007, Int Immunol
TLR9 Plasmodium berghei ANKA C57BL/6 TLR9 -/- yes yes CM CM Similar Similar neurologic symptoms; similar ICAM-1 in brain; similar inflammation in lung; similar hemozoin deposition in liver Togbe et al., 2007, Am J Pathol
TLR9 Plasmodium chabaudi AS C57BL/6 TLR9 -/- no no N.I. N.I. Similar Decreased up-regulation of CD40, CD86 and MHC class II, decreased production of TNF-a and IL-12p70, no degradation of IkB-a and no translocation of NF-kB to the nucleus after incubation of TLR9 -/- DCs with P. berghei or P. chabaudi schizonts; Decreased expression of CD40, CD80 and CD86 on splenic DCs isolated from P. berghei-infected mice 6 days p.i. and P. chabaudi-infected mice 7 days p.i. Seixas et al., 2009, Eur J Immunol
TLR9 Plasmodium chabaudi chabaudi AS C57BL/6 TLR9 -/- no no N.I. N.I. Similar Similar hypothermia and weight loss during peak parasitemia; similar TNF-a and MCP-1 and ↓ IFN-g 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
TLR9 Plasmodium yoelii 17XL C57BL/6 TLR9 -/- 94% 50% N.I. N.I. Variable Similar CD4+CD25+Foxp3+ (Treg) cells in spleen; no activation of Treg cells; ↑ CD62LlowCD69high and IFN-g+ CD4+ cells in spleen; CD4+ cells proliferated in response to pRBC Hisaeda et al., 2008, J Immunol
TLR9 Plasmodium yoelii 17XNL N.I. TLR9 -/- no no N.I. N.I. Similar N.I. Cramer et al., 2008, Microbes Infect
TLR9 Plasmodium yoelii 17XNL C57BL/6 TLR9 -/- no no Anemia Anemia Similar N.I. Hisaeda et al., 2008, J Immunol
TLR9/CD4 Plasmodium yoelii 17XL TLR9 -/- (C57BL/6) anti-CD4 50% yes N.I. N.I. Similar N.I. Hisaeda et al., 2008, J Immunol
TLR9/IFN-g Plasmodium yoelii 17XL TLR9 -/- (C57BL/6) anti-IFN-g 50% yes N.I. N.I. Similar N.I. Hisaeda et al., 2008, J Immunol
TNF Plasmodium chabaudi adami 408XZ C57BL/6J TNF -/- 29% 70% Anemia Anemia Increased peak and increased recrudescences ↓ Hb levels on d4, d12 and d16 p.i.; similar blood glucose and lactate levels except on d7 p.i.; ↓ body temperature on d7, d12, d16 and d25 p.i.; similar body weights except on d4 p.i. Hernandez-Valladares et al., 2006, Exp Parasitol
TNF-a Plasmodium berghei (N.I.) C57BL/6 TNF-a -/- yes N.I. N.I. N.I. N.I. Similar number of CD11c+ DC in the spleen; ↓ expression of MHC II, CD80 and CD86 by splenic CD11c+ DC; CD11c+ DC were better at initiation of proliferation of OTII T cells; ↑ IL-12 secreting DC in the spleen Wykes et al., 2007, J Immunol
TNF-a Plasmodium berghei ANKA CBA/Ca rHu-TNF-a or rMu-TNF-a yes yes CM No CM N.I. No neurological symptoms; no petechial hemorrhages or edema in brain; no monocytes adherence in cerebral vessels; developed hypoglycaemia and midzonal liver necrosis Clark et al., 1992, Am J Pathol
TNF-a Plasmodium berghei ANKA C57BL/6 TNF-a -/- yes yes CM (100%) CM (100%) similar ↓ serum NO3-; similar serum IFN-g, ↓ ICAM-1 and ↓ CR3+ leukocytes in the brain Engwerda et al., 2002, J Exp Med
TNF-a Plasmodium berghei ANKA CBA/Ca anti-TNF-a yes yes CM (79%) CM (6,6%) similar Prolonged survival (1-3 weeks); no neurological symptoms; no macrophage accumulation in brain; ↓ macrophage accumulation in spleen and lymph nodes; similar parasite-specific Ab response Grau et al., 1987, Science
TNF-a Plasmodium berghei ANKA CBA/Ca anti-TNF-a yes N.I. CM (80%) N.I. N.I. ↓ serum IL-6 Grau et al., 1990, J Exp Med
TNF-a Plasmodium berghei ANKA N.I. TNF-a -/- yes yes CM CM N.I. Similar indoleamine 2,3-dioxygenase-1 mRNA expression in the brain Hansen et al., 2004, Int J Parasitol
TNF-a Plasmodium berghei ANKA C57BL/6J TNF-a -/- yes yes CM CM Similar Similar neurologic symptoms; similar levels of [31P]-containing metabolites (phosphomonoesters (PME), inorganic phosphate (Pi), phosphocreatinine (PCr), Pi:b-ATP, Pi:PCr) and ↑ levels (normal values) of b-ATP and PCr:PME in brain 6-7 days p.i.; ↓ GABA, and aspartate, ↑ glutamine and NAA, and similar alanine, lactate and glutamate metabolite pool sizes in brain (compared with uninfected TNF-a -/- mice); similar brain net flux of 13C from D-[1-13C]glucose into metabolic intermediates associated with Krebs cycle (↓ compared to uninfected TNF-a -/- mice), except for Asp C3 and Lac C3 which was not ↓ and Ala C3 which did not change upon infection Parekh et al., 2006, Int J Parasitol
TNF-a Plasmodium berghei ANKA C57BL/6J anti-TNF-a N.I. N.I. N.I. N.I. N.I. Similar number of microparticles in plasma Piguet et al., 2002, Apoptosis
TNF-a Plasmodium berghei ANKA C57BL/6J TNF-a -/- yes yes CM (100%) CM (100%) similar Similar neurologic symptoms: similar ischemic brain damage, brain swelling, edema and vascular blood flow perturbations; no anemia (cfr. WT); similar perforin+CD8+, CD54+CD8+ and CD69+CD8+ T cells in brain; similar lung pathology and edema; similar thickening of alveolar septae Togbe et al., 2008, PLoS One
TNF-a Plasmodium berghei K173 C57BL/6J rHu-TNF-a (↑ dose) yes yes CM TNF toxicity N.I. Died 24 h after injection; hypothermia, brain petechial hemorrhages; ↑ kidney, lung and liver pathology Curfs et al., 1993, Parasitology
TNF-a Plasmodium berghei K173 C57BL/6J rHu-TNF-a (↓ dose) yes yes CM No CM N.I. Prolonged survival (2-3 weeks); no neurological symptoms; no hypothermia; n=3 Curfs et al., 1993, Parasitology
TNF-a Plasmodium berghei K173 C57BL/6J anti-TNF-a yes yes CM (96%) CM (96%) N.I. N.I. Hermsen et al., 1997, Parasite Immunol
TNF-a Plasmodium chabaudi adami 556KA CBA/CaH rHu-TNF-a no no N.I. N.I. Delayed onset and decreased peak N.I. Clark et al., 1987, J Immunol
TNF-a Plasmodium chabaudi chabaudi AS C57BL/6 TNF-a -/- no no Anemia Anemia Similar Similar anemia, serum IFN-g and Ig titers; ↓ serum TNF-a Clark et al., 2007, Parasite Immunol
TNF-a Plasmodium chabaudi chabaudi AS C57BL/6 anti-TNF-a (Mab) no no N.I. N.I. Similar Similar iNOS mRNA expression in spleen 7 days p.i.; partial ↓ NO3- levels in serum 7 days p.i.; ↓ spleen weight 7 days p.i. Jacobs et al. 1996, Infect Immun
TNF-a Plasmodium chabaudi chabaudi AS C57BL/6 anti-TNF-a (PAb) no 50% N.I. N.I. Slightly delayed onset (1 day) N.I. Jacobs et al., 1996, Infect Immun
TNF-a Plasmodium chabaudi chabaudi AS DBA/2 anti-TNF-a 70% 20% Liver pathology No liverpathology Similar ↓ liver apoptosis and necrosis; ↓ plasma AST and ALT; similar blood hemoglobin concentration Seixas et al., 2008, Parasitology
TNF-a Plasmodium chabaudi chabaudi AS DBA/2 anti-TNF-a 75% 25% Liver pathology and severe anemia No liverpathology Similar ↓ plasma AST, ↓ liver portal and central lobular vein necrosis, inhibition of hepatocyte programmed cell death; only the combination of free heme and TNF-a induced free radicals, lipid peroxidation products and apoptosis in hepatocytes in an in vitro assay which was reduced after treatment with anti-oxidantia (BHA, NAC) or by transduction of hepatocytes with an HO-1 expressing adenovirus Seixas et al., 2009, Proc Natl Acad Sci U S A
TNF-a Plasmodium chabaudi chabaudi AS C57BL/6 rHuTNF-a no no N.I. N.I. Similar High doses of rHu-TNF-a resulted in 100 % mortality even at low parasitemia levels Stevenson et al., 1989, Infect Immun
TNF-a Plasmodium chabaudi chabaudi AS A/J rHuTNF-a yes 20% N.I. N.I. Spontaneous decline and clearance Resistant to secondary infection Stevenson et al., 1989, Infect Immun
TNF-a Plasmodium vinckei (N.I.) C57BL/6 TNF-a -/- yes N.I. N.I. N.I. N.I. Similar number of CD11c+ DC in the spleen;↓ expression of MHC II, CD80 and CD86 by splenic CD11c+ DC; similar initiation of proliferation of OTII T cells; ↑ IL-12 secreting DC in the spleen Wykes et al., 2007, J Immunol
TNF-a Plasmodium vinckei vinckei CBA/Ca rHu-TNF-a or rMu-TNF-a yes yes HP&A HP&A N.I. No neurological symptoms; ↑ midzonal liver necrosis and hypoglycemia Clark et al., 1992, Am J Pathol
TNF-a Plasmodium yoelii 17XL C57BL/6 x 129 TNF-a -/- Lethality dependent on parasite dosis, no difference between WT and KO mice Lethality dependent on parasite dosis, no difference between WT and KO mice N.I. N.I. No clearance in 25 days N.I. Shear et al., 1998, Am J Trop Med Hyg
TNF-a Plasmodium yoelii 17XNL C57BL/6 x 129 TNF-a -/- no no N.I. N.I. Increased peak and delayed clearance N.I. Shear et al., 1998, Am J Trop Med Hyg
TNF-a/ IFN-g Plasmodium chabaudi chabaudi AS C57BL/6 anti-TNF-a + anti-IFN-g no no N.I. N.I. Increased peak ↓ iNOS mRNA expression in spleen 7 days p.i.; ↓ NO3- levels in serum (synergy) 7 days p.i.; ↓ spleen weight 7 days p.i. Jacobs et al. 1996, Infect Immun
TNF-a/ LT-a Plasmodium berghei ANKA C57BL/6 TNF-a -/- x LT-a -/- yes yes CM (100%) No CM Similar Prolonged survival (days); no neurological symptoms; ↓ serum NO3- and IFN-g; ↓ ICAM-1 and CR3+ leukocytes in the brain Engwerda et al., 2002, J Exp Med
TNF-a/ LT-a Plasmodium berghei ANKA 129/Sv/Ev x C57BL/6 TNF-a -/- x LT-a -/- yes yes CM (100%) No CM similar Prolonged survival (1-2 weeks); no neurological symptoms; similar anemia; slightly ↑ leukocytosis; no leukocyte accumulation in brain; ↓ ICAM-1 + CD11b in brain; ↓ serum NO; ↓ IFN-g and no IL-12 , IL-10 and IL-4 mRNA expression in the brain; similar IFN-g, IL-12, IL-10 and no IL-4 mRNA expression in the spleen Rudin et al., 1997, Am J Pathol
TNFR1 Plasmodium berghei ANKA C57BL/6 Tg + soluble TNFR1 yes yes CM (80%) CM (20-30% in high expressor mice); CM (100% in low expressor mice) similar Prolonged survival in high-expressor mice (~2 weeks); no neurological symptoms Garcia et al., 1995, Eur J Immunol
TNFR1 Plasmodium berghei ANKA C57BL/6 x 129 TNFR1 -/- yes yes CM (90%) CM (78%) similar Similar neurologic symptoms; similar serum IFN-g, TNF-a and sTNFR2; similar ICAM-1 expression on endothelial cells and sequestering leukocytes in the brain; induction of ICAM-1 expression in MVEC through binding of membrane-bound mTNF-a (but not soluble mTNF or membrane-bound hTNF) with TNFR2 Lucas et al., 1997, Eur J Immun
TNFR1 Plasmodium berghei ANKA C57BL/6 x 129 TNFR1 -/- yes yes CM (90%) CM (78%) similar Similar neurologic symptoms and lung pathology; similar serum IFN-g and TNF-a; similar ICAM-1 endothelial expression in brain and lung Lucas et al., 1997, J Neuroimmunol
TNFR1 Plasmodium berghei ANKA C57BL/6J TNFR1 -/- yes yes CM CM similar Similar TNF-a, CD40 and ICAM-1 in brain; ↓ vascular leakage in brain and lung; similar BBB breakdown, macrophage accumulation in brain, hyperglycemia, insulin resistance, hypothermia, edema, thrombocytopenia and lung weight; enlarged basement membrane of brain capillaries in KO mice Piguet et al., 2002, Lab Invest
TNFR1 Plasmodium berghei ANKA C57BL/6J TNFR1 -/- yes yes CM (100%) CM (100%) N.I. Similar neurologic symptoms Togbe et al., 2008, PLoS One
TNFR2 Plasmodium berghei ANKA C57BL/6 TNFR2 -/- N.I. N.I. N.I. N.I. N.I. ICAM-1 increased on d4 and similar on d6 in brain; increased on d4-6 in lungs Bauer et al., 2002, Microcirculation
TNFR2 Plasmodium berghei ANKA C57BL/6 x 129 TNFR2 -/- yes yes CM (90%) CM (10%) similar Prolonged survival (weeks); no neurological symptoms; similar serum IFN-g, TNF-a and sTNFR1; no ↑ in ICAM-1 expression on brain endothelial cells; no sequestration of leukocytes in the brain; no induction of ICAM-1 expression in MVEC after stimulation with soluble or membrane-bound mTNF or membrane-bound hTNF Lucas et al., 1997, Eur J Immun
TNFR2 Plasmodium berghei ANKA C57BL/6 x 129 TNFR2 -/- yes yes CM (90%) CM (10%) similar Prolonged survival (2-3 weeks); no neurological symptoms; similar serum IFN-g and TNF-a; similar lung pathology;↓ ICAM-1 endothelial expression in brain and similar ICAM-1 in lungs Lucas et al., 1997, J Neuroimmunol
TNFR2 Plasmodium berghei ANKA C57BL/6 TNFR2 -/- yes yes CM No CM similar No hypothermia, hyperglycemia or coma; ↓ vascular permeability in brain and lung; similar thrombocytopenia and lung weight; similar leukocyte sequestration in brain; ↓ macrophage accumulation and similar pRBC sequestration in alveolar capillaries; similar TNF-a, CD40 and ICAM-1 mRNA expression in brain and spleen; similar TNF-a, CD40 and ↓ ICAM-1 in lung; insulin sensitive (mice died of hypoglycemia after insulin injection) Piguet et al., 2002, Lab Invest
TNFR2 Plasmodium berghei ANKA C57BL/6 TNFR2 -/- yes yes CM (90%) CM (25%) Similar Prolonged survival (2-3 weeks); no neurological symptoms; no platelet staining in brain Stoelcker et al., 2002, Infect Immun
TNFR2 Plasmodium berghei ANKA C57BL/6 TNFR2 -/-bone marrow cells yes yes CM (90%) CM (90%) Similar Similar neurologic symptoms Stoelcker et al., 2002, Infect Immun
TNFR2 Plasmodium berghei ANKA TNFR2 -/- WT bone marrow cells yes yes CM (25%) CM (50%) Similar Prolonged survival (2-3 weeks); no neurological symptoms Stoelcker et al., 2002, Infect Immun
TNFR2 Plasmodium berghei ANKA C57BL/6 TNFR2 -/- yes yes CM (100%) CM (10%) N.I. No neurologic symptoms Togbe et al., 2008, PLoS One
TRIF Plasmodium berghei ANKA 129/Ola x C57BL/6 TRIF -/- yes yes CM (91%) CM (100%) Similar Similar red blood cell and leukocyte sequestration in brain microvasculature; similar endothelial cell detachment; similar granzyme B, CCL3 and lipocalin-2 mRNA in brain; Similar serum IL-12p40, IFN-g and TNF-a Coban et al., 2007, Int Immunol
TRIF Plasmodium berghei ANKA C57BL/6 TRIF -/- yes yes CM (100%) CM (100%) Similar N.I. Togbe et al., 2007, Am J Pathol
TRIF Plasmodium yoelii 17XNL N.I. TRIF -/- no no N.I. N.I. Similar Similar serum IL-12p40 6 days p.i. Cramer et al., 2008, Microbes Infect
uPA receptor (uPAR, CD87) Plasmodium berghei ANKA C57BL/6 x 129/Sv uPAR -/- yes yes CM (80%) CM (20%) Similar Prolonged survival (~1 week) ; ↓ thrombocytopenia; slightly ↓ platelet life span (similar to noninfected uPAR -/- mice); slightly ↑ fibrinogen half-life; ↑ splenomegaly; no ↑ in lung weight; similar TNF-a mRNA in spleen, lung and brain; similar leakage of Evans Blue in brain and lung; ↓ platelet trapping in alveolar and brain capillaries; similar PMN, macrophage and pRBC sequestration in alveolar capillaries; similar mononuclear leukocytes in brain microvasculature Piguet et al., 2000, Infect Immun

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