. 2011 Nov 11;6(11):e27131. doi: 10.1371/journal.pone.0027131

Table 1. Overview of the genetic background of TLR9^−/− mice in experimental malaria infections.

CONTROL STRAIN		KNOCKOUT STRAIN		TLR9 knockout phenotype	Ref.
Source	Breeding information	Source	N° of backcross generations to the WT background
*Plasmodium chabaudi* AS
B6.WT(?) + PcAS	undefined	B6.TLR9^−/−(?)+PcAS	undefined	no difference in parasitemia, in body weight and in temperature, ↓ production of IFN-γ by splenocytes on day 8 pi	[36]
B6.WT (local breeding facility) + PcAS	undefined (^*pure local C57Bl/6 line)	B6.TLR9^−/− (Prof. Akira,Japan)^a+PcAS	undefined (^*at least 8–9× on local inbred line)	no difference parasitemia, no difference in the alterations in splenic microarchitecture	[37]
B6.WT(JL) (DCs) + PcAS	according to commercial breeder strategy [75]	B6.TLR9^−/− (Prof. Akira,Japan)^a (DCs)+PcAS	at least 8×	no difference in parasitemia, ↓ TLR upregulation, ↓ production of IFN-γ/IL-12 by splenocytes/ DCs, ↑ resistance against LPS-induced mortality	[15]
B6.WT (?, ^*local breeding facility) (pDCs) + PcAS	undefined (^*pure local C57Bl/6 line)	B6.TLR9^−/− (Prof. Akira,Japan)^a (pDCs)+PcAS	10×	↓ IFN-γ production in co-culture of pDC+iRBC, ↓ IFN-γ mRNA in pDC on day 3 pi, no difference in parasitemia, body weight and temperature	[38]
B6.WT (local breeding facility) (DCs) + PcAS or PbANKA	undefined	B6.TLR9^−/− (Prof. Akira,Japan)^a (DCs)+PbANKA or PcAS	undefined	↓ DC activation by parasites, no nuclear translocation of NF-κB in DCs, no difference in parasitemia (PcAS), ↓ in vivo activation of splenic DCs, ↑ IgM on day 10 pi (PcAS)	[35]
*Plasmodium berghei* ANKA
B6.WT(?) + PbANKA	undefined	B6.TLR9^−/− (Prof. Akira,Japan)^a+PbANKA	at least 10×	↓ macrophage response to pRBCs, no difference in parasitemia, in lung and hepatic pathology, in CM development and in survival	[23]
B6.WT(JL) + PbANKA	according to commercial breeder strategy [75]	B6.TLR9^−/−(?)+PbANKA	at least 7×	no difference in parasitemia, ↑ survival, ↓ CM	[18]
B6.WT (CLEA, Japan) + PbANKA	according to commercial breeder strategy [76]	B6.TLR9^−/− (Prof. Akira,Japan)^a + PbANKA	at least 8×	no difference in parasitemia, ↑ survival, ↓CM	[22]
B6.WT (?, ^*local breeding facility) + PbANKA	undefined (^*pure C57Bl/6 from local breeding facility)	TLR2/4/9^−/−(Kirschning,Munich)^b + PbANKA	mixed (129SVxC57Bl/6)	no difference in parasitemia, CM development and survival	[24]
*Plasmodium yoelii*
B6.WT (Kyudo,Japan) + P. yoelii	undefined	B6.TLR9^−/− (Prof. Akira,Japan)^a + P. yoelii	at least 15×	partial resistance to lethal infection (parasitemia, survival), ↓ activation of Tregs by DCs, ↑ activation of CD4⁺ T cells	[68]
Balb/c.WT (CLEA Japan) + immunization with baculovirus-based PyMSP1₁₉ + P. yoelii 17XL	according to commercial breeder strategy [76]	Balb/c.TLR9^−/− (Prof. Akira,Japan) + immunization with baculovirus-based PyMSP1₁₉ + P. yoelii 17XL	undefined	vaccine induced protection abolished, ↑ Th₂ immune responses	[77]
*Parasite components*
B6.WT (CLEA Japan): DCs + schizont extracts	according to commercial breeder strategy [76]	B6.TLR9^−/− (Prof. Akira,Japan)^a: DCs+schizont extracts	8×	↓ schizont-induced DC activation	[27]
B6.WT (?, ^*CLEA Japan) (DCs) + n/sHz	undefined (^*according to commercial breeder strategy [76])	B6.TLR9^−/− (Prof. Akira,Japan)^a (DCs) + n/sHz	undefined (^*at least 8×)	↓ innate immune activation by n/sHz	[28]
B6.WT(JL): DCs + n/sHz	according to commercial breeder strategy [75]	B6.TLR9^−/− (Prof. Akira,Japan)^a: DCs + n/sHz	more than 10× (genetic background analyzed by microsatellite analysis (Charles River Laboratories))	↓ innate immune activation by plasmodial DNA on Hz	[31]
B6.WT(JL) (macrophages) + sHz	according to commercial breeder strategy [75]	B6.TLR9^−/− (Prof. Akira,Japan)^a (macrophages) + sHz	9×	no difference in inflammatory response to sHz	[78]
B6.WT (?, ^*CLEA Japan) + Pf crude extract or + sHz	undefined (^*according to commercial breeder strategy [76])	B6.TLR9^−/− (Prof. Akira,Japan)^a + Pf crude extract or + sHz	undefined (^*at least 8×)	↓ adaptive immune responses after Pf crude extract immunization, no difference in potent adjuvanticity of sHz	[30]
B6.WT(JL): DCs + parasite components	according to commercial breeder strategy [75]	B6.TLR9^−/− (Prof. Akira,Japan)^a: DCs + parasite components	undefined	↓ activation of DCs by MZs and iRBCs	[79]
B6.WT (?, ^*JL): DCs + polynucleosomes	undefined (^*according to commercial breeder strategy [75])	B6.TLR9^−/−( Prof. Akira,Japan): DCs + polynucleosomes	undefined (^*several x)	little or no activation of DCs by polynucleosomes	[32]

Generated by Hemmi et al. [70].

Generated by Yasuda et al. [80].

Personal communication.

↑, increased; ↓, decreased; B6, C57Bl/6; DCs, dendritic cells; CM, cerebral malaria; (p)DCs, (plasmacytoid) dendritic cells; (n/s)Hz, (natural/synthetic) hemozoin; iRBCs, infected red blood cells; JL, Jackson Laboratory; MZs, merozoites; NF-κB, nuclear factor κ-light-chain-enhancer of activated B cells; PbANKA, Plasmodium berghei ANKA; PcAS, Plasmodium chabaudi chabaudi AS; Pf, Plasmodium falciparum; PyMSP1₁₉, Plasmodium yoelii 19 kDa carboxyl terminus of merozoite surface protein 1; TLR9, toll-like receptor 9; Tregs, regulatory T cells.

Table 1. Overview of the genetic background of TLR9−/− mice in experimental malaria infections.

Table 1. Overview of the genetic background of TLR9^−/− mice in experimental malaria infections.