ライフサイエンスコーパス: L. major

1 L. major expresses two nucleobase permeases, NT3 that is

2 L. major infection enhanced N-Ras activity but inhibited

3 L. major infection is associated with self-limiting cuta

4 L. major MTHFR was expressed in yeast and recombinant en

5 L. major-exposed keratinocytes had no comparable effect.

6 recombinant murine interleukin-12 (rmIL-12), L. major SEAgs coadministered with both alum and rmIL-12

7 A L. major null mutant, Deltalmgat/Deltalmgat, was created

8 We have studied a L. major strain from a patient with nonhealing lesions t

9 compared to wild-type (WT) littermates after L. major infection.

10 led to mount an efficient Th1 response after L. major infection, produced more IL-4, and developed la

11 emination of parasites into the spleen after L. major infection.

12 transferred into mice at various times after L. major infection to determine the duration of presenta

13 vity of CTZ by factors of 110 and 58 against L. major and T. cruzi, with no appreciable toxicity to h

14 ls plays a critical role in immunity against L. major by controlling the migration of Th1 cells to th

15 ine receptor CXCR3 mediates immunity against L. major by recruiting IFN-gamma-producing T cells to th

16 the induction of protective immunity against L. major by regulating IL-12p70 production and migration

17 CD8(+) T cells in mediating immunity against L. major by transferring T cells from wild-type (WT) and

18 to become Th1 cells and protect mice against L. major following adoptive transfer into STAT1-sufficie

19 development of Th1 cells protective against L. major and instead stress the importance of STAT1 sign

20 tion of a protective T cell response against L. major infections.

21 ce were immunized with L. major SEAgs alone, L. major SEAgs coadministered with either alum (aluminum

22 and Dice1.2, respectively, also contained an L. major response locus, indicating that L. major respon

23 d with liposomal amphotericin B (LAmB) in an L. major mouse model and analyzed the therapeutic effica

24 racterized the expression and function of an L. major phosphatase, which we termed LmPRL-1.

25 administered with both alum and rmIL-12, and L. major SEAgs coadministered with Montanide ISA 720.

26 ng lymph node cells from L. amazonensis- and L. major-infected mice at 10 weeks postinfection showed

27 oinoculated with trimannose-coated beads and L. major Trimannose treatment of L. major-infected mice

28 r alone, coinoculated with carrier beads and L. major, or coinoculated with trimannose-coated beads a

29 ctural differences between the T. brucei and L. major enzymes.

30 Comparisons of T. brucei with T. cruzi and L. major indicate a high degree of conservation among th

31 controlling naive T cell Il4 expression and L. major responses, and for testing whether these contro

32 observed that Leishmania-infected humans and L. major-infected C57BL/6 mice exhibited substantial amo

33 These data suggest that L. infantum and L. major differentially activate keratinocytes to releas

34 nia, L. tarentolae, Leishmania infantum, and L. major, produced hypersensitivity to both As(III) and

35 proliferating in response to L. mexicana and L. major.

36 L. tarentolae and L. major genome annotation was transferred and these gen

37 plete resolution of chronic lesion in arg(-) L. major-infected mice.

38 hese results show that infection with arg(-) L. major results in chronic disease due in part to PD-1-

39 ce infected with arginase-deficient (arg(-)) L. major failed to completely resolve their lesion and m

40 However, as L. major infection typically progress over weeks to mont

41 sion and RNA processing events that occur as L. major transforms from non-infective procyclic promast

42 e killing of intracellular pathogens such as L. major, or a type 2 response, leading to antibody prod

43 tive against intracellular pathogens such as L. major.

44 teomic and immunoblot analyses of attenuated L. major strains deficient for LACK, the Leishmania orth

45 DC with caffeic acid phenethyl ester blocks L. major-induced IRF-1 and IRF-8 activation and IL-12 ex

46 may shed light on the mechanisms employed by L. major to survive in the absence of LPG2-dependent gly

47 of T-bet did not prevent IL7R expression by L. major-responding CD4(+) T cells, nor did the absence

48 These findings showed that IDO induced by L. major infection attenuated innate and adaptive immune

49 Here, we report that DC priming by L. major infection results in the early activation of NF

50 uggest that proteins secreted or released by L. major in infected DC are a major source of peptides f

51 glf-1 mutants rescued by L. major glf, which behave as glf-1 hypomorphs, display

52 cate a novel immune escape mechanism used by L. major parasites in the absence of IL-4/IL-13 signalin

53 Second, a reduced number of LCs carried L. major from the skin to the draining lymph nodes in Cc

54 secrete the extracellular portion of CD40L (L. major CD40LE).

55 ajor protected BALB/c mice against challenge L. major infection; the protection was accompanied by lo

56 or cells can express the IL7R during chronic L. major infection, which provides a potential means for

57 Distinct from chronic L. major infection, IL-10 blockade alone had no effect o

58 to produce sufficient amounts of NO to clear L. major.

59 rol and heightened mortality after T. cruzi, L. major, and Toxoplasma gondii infection, despite an ap

60 nerate null TOR1 or TOR2 mutants in cultured L. major promastigotes.

61 B6.WT mice over the first 2 wk of cutaneous L. major infection.

62 fection site and were resistant to cutaneous L. major infection.

63 ession of LmCOX subunit IV in LACK-deficient L. major restored thermotolerance and macrophage infecti

64 unction were also impaired in LACK-deficient L. major under these conditions.

65 nce tests it closely resembled LPG-deficient L. major, including sensitivity to complement and an ina

66 the IL7R on CD4(+) T cells activated during L. major infection.

67 fferentiation of protective Th1 cells during L. major infection, IFN-gammaR and STAT1 are dispensable

68 velopment of inappropriate Th17 cells during L. major infection.

69 not required for Th1 differentiation during L. major infection.

70 ry CD4(+) T cell population generated during L. major infection is capable of developing into either

71 nd lesions of BALB/c and C57BL/6 mice during L. major infection.

72 the specific IL-12 induction observed during L. major infection remains to be thoroughly elucidated.

73 dermis at steady-state conditions or during L. major infection express the alpha(E) chain (CD103) of

74 ) mice fail to develop a Th1 response during L. major infection.

75 ution of local inflammatory responses during L. major infection.

76 These results suggest that during L. major infection Ag-experienced T cells, rather than n

77 ell genes and pathways associated with early L. major infection in human myeloid-derived DCs.

78 nt with anti-IL-10R mAb virtually eliminated L. major parasites in both footpad and dermal infection

79 iasis in a mouse model, while also enhancing L. major specific T-cell immune responses in the infecte

80 doptive transfer of WT CD4(+) T cells or few L. major primed WT T(FH) cells reconstituted GC formatio

81 administration during the priming with fixed L. major protected BALB/c mice against challenge L. majo

82 he early generation of T(CM) cells following L. major infection indicates that T(CM) cells may not on

83 a deficit in lymph node expansion following L. major infection, as well as increased susceptibility.

84 e show that lymph node hypertrophy following L. major infection in mice is associated with increased

85 l)phenyl)cinnolin-4-amine (NEU-1017, 68) for L. major and P. falciparum.

86 mice, revealing that PKR is dispensable for L. major growth in macrophages.

87 s establish a requirement for GDP-fucose for L. major viability and predict the existence of an essen

88 ibility to L. mexicana infection, unlike for L. major infection.

89 When lymphoid cells from L. major SEAg-immunized mice were stimulated with leishm

90 Restimulated lymph node cells from L. major-infected BALB/c-CXCR3(Tg) mice produced more in

91 5% of the IFN-gamma produced by T cells from L. major-infected mice under identical conditions.

92 Furthermore, T cells from L. major-susceptible BALB/c but not L. major-resistant C

93 d recombinant RNA editing exonuclease I from L. major, and recombinant RNA editing RNA ligase 1 from

94 monstrate that IRF-1 and IRF-8 obtained from L. major-infected human DC specifically bind to their co

95 NAD(P)H cytochrome b(5) oxidoreductase from L. major (LmNcb5or) knock-out mutants by targeted gene r

96 To test this hypothesis, we generated L. major parasites that express a mutated LACK that fail

97 served that ectopic expression of LmPRL-1 in L. major led to an increased number of parasites in macr

98 of IL-10 that disrupts IFN-gamma activity in L. major-susceptible BALB/c mice.

99 sites within polycistronic gene clusters in L. major leads to read through transcription and increas

100 ntigens to specific cellular compartments in L. major and suggest that proteins secreted or released

101 CMV led to significantly enhanced disease in L. major-infected animals.

102 One allele of LmAQP1 was disrupted in L. major, and the resulting cells became 10-fold more re

103 Truncated OVA was expressed in L. major as part of a secreted or nonsecreted chimeric p

104 indicating TLR2-regulated Ras expression in L. major infection.

105 Corroborating these findings, in L. major-infected macrophages, CD40-induced SHP-1 phosph

106 on profile for several IFN response genes in L. major versus L. donovani DC infections.

107 I-PLCp caused a deficiency of protein-GPI in L. major, whereas glycosomal GPI-PLCp failed to produce

108 capability in T. brucei and the greatest in L. major.

109 Reduction of J in L. major resulted in genome-wide defects in transcriptio

110 h a requirement for 10-CHO-THF metabolism in L. major, and provide genetic and pharmacological valida

111 TLR2-TLR6 ligand) reduced L. major number in L. major-infected macrophages, accompanied by increased

112 , suggesting a potential role for CpG ODN in L. major treatment.

113 e response and subsequent disease outcome in L. major-infected mice.

114 ot attached to macromolecules are present in L. major as intermediates of protein-GPI and polysacchar

115 d that two of these molecules are present in L. major SEAgs, lipophosphoglycan and the molecules that

116 njugates had not been reported previously in L. major, but unexpectedly, we were unable to generate f

117 shows homology to another editing protein in L. major, which lacks the EEP motif (LmREX2*).

118 t for biogenesis of GPI-anchored proteins in L. major; (ii) sequestration of GPI-PLCp to glycosomes p

119 of homologs of the 9-1-1 complex subunits in L. major and found that LmRad9 and LmRad1 associate with

120 Tests in L. major using dd fusions to a panel of reporters and ce

121 An analysis of genomic UTRs in L. major showed that (i) the consensus APR is N(-3)N(-2)

122 d) and peptidoglycan (TLR2 ligand) increased L. major infection but reduced TLR9 expression, whereas

123 nistration reduced, but TLR6-shRNA increased L. major infection in BALB/c mice.

124 ion, Bim-/- mice had significantly increased L. major-specific CD4+ T-cell responses and were resista

125 short hairpin RNA enhanced the CD40-induced L. major parasite killing in susceptible BALB/c mice.

126 s from Leishmania braziliensis, L. infantum, L. major, L. tarentolae, Trypanosoma brucei and T. cruzi

127 sed to probe trafficking of GPI pools inside L. major.

128 esions, and these monocytes efficiently kill L. major parasites.

129 ajor infection, vaccination with heat-killed L. major plus CpG and SB203580 elicited complete protect

130 against infection compared with heat-killed L. major plus CpG without SB203580.

131 ation with whole-cell lysates of heat-killed L. major promastigotes bound to alum (ALM).

132 rotection conferred by vaccination with live L. major organisms in C57BL/6 mice.

133 may also improve the potential of the lpg2- L. major line to serve as a live parasite vaccine by ove

134 , we show that a strain of Leishmania major (L. major Seidman [LmSd]) that produces nonhealing cutane

135 h resistance to developing Leishmania major (L. major) infection.

136 ifferential expression data for L. mexicana, L. major and Leptomonas seymouri, we have identified sev

137 nd effector CD4 T-cell formation in mif(-/-) L. major-infected mice when compared to mice infected wi

138 lyses revealed a reduced ability of mif(-/-) L. major to activate antigen-presenting cells, resulting

139 hat developed during infection with mif(-/-) L. major demonstrated statistically significant differen

140 Mice infected with mif(-/-) L. major, when compared to the wild-type strain, also sh

141 1 response during the course of a nonhealing L. major infection through a mechanism that is independe

142 lls from L. major-susceptible BALB/c but not L. major-resistant C57BL/6 mice fail to efficiently upre

143 , we tested the infectivity of a new PG-null L. major mutant, which is inactivated in the two UDP-gal

144 The ability of L. major transgenic parasites to activate OT-I CD8(+) T

145 Analysis of L. major-infected BALB/c and IL-4Ralpha(-/-) inflammator

146 or early IFN-gamma production and control of L. major.

147 DM-sufficient APC, may change the course of L. major infection in the susceptible BALB/c mice.

148 thus offer a route to the rational design of L. major-specific GLO1 inhibitors.

149 merase chain reaction tests for detection of L. major.

150 TAT1 in preventing systemic dissemination of L. major infection.

151 d predominantly in the insect vector form of L. major, and immunofluorescence demonstrated that LmPOT

152 we used sand fly-derived metacyclic forms of L. major and preexposed the injection site to the bites

153 more potent linear competitive inhibitor of L. major than human GLO1 (Kis of 0.54 microM and 12.6 mi

154 Injection of L. major-activated dendritic cells promoted lymph node h

155 l animals at 2 wk post-needle inoculation of L. major, and this correlated with a 100-fold reduction

156 cessfully resolve infection by an isolate of L. major, despite a strong IFN-gamma response by the hos

157 responses that contribute to the killing of L. major.

158 surface-expressed and secreted molecules of L. major (lipophosphoglycan, gp46/M2/PSA-2, and gp63) re

159 against leishmanolysin-knock out mutants of L. major.

160 with a significant increase in the number of L. major-specific IFN-gamma-producing CD4+ T cells and a

161 and TNF-alpha in determining the outcome of L. major infection beyond a balance between Th1- and Th2

162 CR3 on T cells did not impact the outcome of L. major infection in C57BL/6 mice, which mounted a pred

163 mechanisms resulting in the fatal outcome of L. major infection in this gene-deficient mouse strain,

164 Fifty percent of L. major-knockout lines for the ecotin-like serine pepti

165 mutant did not recapitulate the phenotype of L. major lpg2(-), instead resembling the L. major lipoph

166 We have analyzed the potential of L. major transgenic parasites, expressing the model anti

167 We found that resolution of L. major infection in C57BL/6 mice was associated with a

168 , in macrophages impaired the restriction of L. major replication in C57BL/6, but did not affect para

169 nt Leishmania species, a cutaneous strain of L. major and a visceral strain of Leishmania infantum, e

170 ere removed to produce an mif(-/-) strain of L. major This mutant strain replicated normally in vitro

171 The crystal structure of L. major GLO1 reveals differences in active site archite

172 When the substrain of L. major, LV39, was infected, lack of galectin-3 impaire

173 d beads and L. major Trimannose treatment of L. major-infected mice decreased the parasite load and s

174 rovide a substantially more detailed view of L. major biology that will inform the field and potentia

175 In a high-content imaging assay on L. major-infected intraperitoneal mice macrophages, comp

176 te the pleiotropic effects that IL-27 has on L. major-driven Th1, Th2, and Th17 development, and rein

177 following stimulation with LPS/IFN-gamma or L. major.

178 , neutrophil migration, induced by the other L. major substrain, Friedlin, was unaffected, and the in

179 ozoa Leishmania major produces a peroxidase (L. major peroxidase; LmP) that exhibits activities chara

180 In response, L. major produces a peroxidase, L. major peroxidase (LmP), that helps to protect the par

181 r in Bim-/- and wild-type mice after primary L. major infection.

182 n-presenting cell requirement during primary L. major infection using a mouse model in which MHC II,

183 stingly, despite their resistance to primary L. major infection, Bim-/- mice displayed significantly

184 ralization of IL-18 in these animals reduced L. major titers and footpad swelling.

185 ce primed with these macrophages had reduced L. major infection, accompanied by higher IFN-gamma but

186 teine (BPPcysMPEG; TLR2-TLR6 ligand) reduced L. major number in L. major-infected macrophages, accomp

187 Both the cell-permeable peptides reduced L. major infection in BALB/c mice but not in CD40-defici

188 Whereas N-Ras silencing reduced L. major infection, K-Ras and H-Ras silencing enhanced t

189 iously, we characterized two closely related L. major genes (FKP40 and AFKP80) encoding bifunctional

190 In response, L. major produces a peroxidase, L. major peroxidase (LmP

191 nals failed to disrupt the early restrictive L. major infection site, which suggests that L. major do

192 f infection-induced immunity after secondary L. major challenge.

193 ilure to induce protection against secondary L. major challenge.

194 rm immunity, and were resistant to secondary L. major challenge, treated CD40L KO reactivated their l

195 1B, whereas keratinocytes exposed to several L. major isolates did not.

196 ction against a genetically diverse species, L. major.

197 ages in vivo compared with a healing strain (L. major Friedlin V1).

198 In kinetic studies L. major and human enzymes were active with methylglyoxa

199 sets is sufficient to control a subcutaneous L. major infection.

200 ture of LmP in a complex with its substrate, L. major cytochrome c (LmCytc) to 1.84 A, and compared t

201 is >4000-fold more active against human than L. major GLO1 (Kis of 0.13 microM and >500 microM respec

202 serine; these studies also established that L. major promastigotes require serine for optimal growth

203 es on the IL-12p35 promoter, indicating that L. major infection either directly stimulates a signalin

204 an L. major response locus, indicating that L. major responsiveness can be insensitive to determinan

205 We observed that L. major enhanced N-Ras and H-Ras expression but inhibit

206 Our data revealed that L. major, but not L. donovani, induces expression of IRF

207 These data show that L. major infection initiates enhanced vascular endotheli

208 L. major infection site, which suggests that L. major dominantly modifies the local milieu.

209 lished biological observations suggests that L. major has a relatively slow growth rate and can repli

210 As the L. major TyrRS pseudo-dimer is inherently asymmetric, co

211 -dependent metabolite is responsible for the L. major amastigote virulence defect, although further s

212 revealed the four subunits of the GCC in the L. major genome, and the role of the GCC in parasite met

213 ining revealed 12 candidate NST genes in the L. major genome, including LPG2 as well as a candidate e

214 lack of general transcription factors in the L. major, Trypanosoma brucei, and Trypanosoma cruzi (Tri

215 IL-12p40 during DC infection, indicating the L. major-induced expression of IL-12p40 is dependent upo

216 Correspondingly, null mutants of the L. major GDP-mannose transporter LPG2 lack PGs and are s

217 roxyacetone phosphate acyltransferase of the L. major localized in the peroxisome, important for grow

218 tified a partial revertant population of the L. major lpg2- mutants (designated lpg2(-)REV) that had

219 The biochemical characterization of the L. major phosphatase revealed that the enzyme is redox s

220 an epitope in the amino-terminal end of the L. major surface gp63 zinc metalloproteinase (leishmanol

221 of L. major lpg2(-), instead resembling the L. major lipophosphoglycan-deficient lpg1(-) mutant.

222 These data reveal the L. major-enhanced CD40-induced N-Ras activation as a nov

223 2 or anti-lipophosphoglycan Abs reversed the L. major-altered N-Ras and K-Ras expressions.

224 From these data, we conclude that the L. major phosphatase LmPRL-1 contributes to the intracel

225 MAX was also added to L. major-infected mouse peritoneal exudate cells (PECs),

226 In comparison to L. major controls, L. amazonensis-infected DCs secreted

227 on T cells in BALB/c mice may contribute to L. major susceptibility.

228 monstrate that this activity is essential to L. major promastigotes, the parasite forms found in the

229 sMPEG conferred antileishmanial functions to L. major-infected BALB/c-derived T cells in a macrophage

230 rmis, but only IL-4-producing cells homed to L. major-infected dermis.

231 Thus, immunity to L. major is mediated by at least two distinct population

232 ufficient to maintain protective immunity to L. major.

233 1 enhanced the susceptibility of the mice to L. major infection, and aggravated inflammatory response

234 s increases susceptibility of BALB/c mice to L. major.

235 Unc93b1(-/-) cells were highly permissive to L. major replication.

236 ction of the susceptible type 2 phenotype to L. major infection.

237 lopment of a TH1 response, and resistance to L. major infection in resistant C57BL/6 mice.

238 CXCR3 on T cells would enhance resistance to L. major infection in susceptible BALB/c mice.

239 scribed endosomal TLR-mediated resistance to L. major infection.

240 hagy contributes to macrophage resistance to L. major replication, and mechanistically explain the pr

241 dless of CD11b status, develop resistance to L. major.

242 T(CM) cells, CD62L(low) cells responding to L. major infection expressed the IL7R.

243 on, which are frequently seen in response to L. major infection.

244 s not bias the T helper cytokine response to L. major infection.

245 iled to participate in the GC in response to L. major or influenza virus infection.

246 ogenous IL-12 reversed the susceptibility to L. major infection in Ccr2(-/-) mice.

247 genes that underlie BALB/c susceptibility to L. major infections are poorly defined.

248 BALB/c mice are susceptible to L. major and show a nonprotective immunodominant CD4 T c

249 -9 (Tlr3/7/9(-/-)) are highly susceptible to L. major infection.

250 knockout (KO) mice are highly susceptible to L. major, treatment with rIL-12 during the first 2 wk of

251 n the present study, we developed transgenic L. major organisms which express and secrete the extrace

252 ffered no protection to subsequent wild-type L. major challenge, suggesting that the transgenic paras

253 a time when the lesion induced by wild-type L. major is completely resolved.

254 hen compared to mice infected with wild-type L. major Notably, effector CD4 T cells that developed du

255 major, yet inoculation with live, wild-type L. major remains the only successful vaccine in humans.

256 or newer epitopes not presented by wild-type L. major-infected APC.

257 es was similar to that elicited by wild-type L. major.

258 against subsequent infection with wild-type L. major.

259 r IFN-gamma response compared with wild-type L. major.

260 tamicin and paromomycin alone for ulcerative L. major disease.

261 , and 9, UNC93B1, or MyD88 failed to undergo L. major-induced autophagy.

262 ial for immunity against L. donovani, unlike L. major.

263 organisms protect BALB/c mice from virulent L. major challenge.

264 ir ability to provide protection to virulent L. major challenge.

265 pg2- parasites were challenged with virulent L. major they were protected from disease.

266 itu hybridization was performed to visualize L. major parasites in fecal samples from the gorillas.

267 When L. major skin lesions of self-healing C57BL/6 mice reach

268 Moreover, when L. major was transfected with a cosmid expressing multip

269 midine hemithioacetal is 40-fold better with L. major GLO1, whereas glutathione hemithioacetal is 300

270 Infection of mammalian cells with L. major modestly decreased IFNAR1 levels and attenuated

271 ination with GLA-SE following challenge with L. major by needle or infected sand fly bite in resistan

272 consistent protection against challenge with L. major was seen in mice immunized with L. major SEAgs

273 y enhanced protection against challenge with L. major.

274 e in susceptible BALB/c mice challenged with L. major promastigotes was investigated.

275 ity responses in immune mice challenged with L. major, indicating that IL7R signaling contributes to

276 d interleukin-12p40 production compared with L. major infection of these same mice.

277 ion after 4 hours of infection compared with L. major infection, which correlated with promastigote t

278 ith L. major was seen in mice immunized with L. major SEAgs alone, in the absence of any adjuvant.

279 Groups of BALB/c mice were immunized with L. major SEAgs alone, L. major SEAgs coadministered with

280 Mice immunized with L. major SEAgs had significantly smaller lesions that at

281 d or carrier (uncoated) beads, infected with L. major alone, coinoculated with carrier beads and L. m

282 When MR(-/-) mice were infected with L. major and treated with trimannose beads, they did not

283 Mice infected with L. major exhibit similar changes depending upon disease

284 rowth in IL-4R alpha(-/-) mice infected with L. major IR173.

285 cells (DC) but not macrophages infected with L. major that secreted NT-OVA could prime OT-I T cells t

286 Here we found that macrophages infected with L. major undergo autophagy, which effectively accounted

287 f optimal Th1 immunity in mice infected with L. major.

288 mB-3 unexpectedly exacerbated infection with L. major (it increased the cutaneous lesion size and the

289 Infection with L. major LV39 but not Friedlin induced higher levels of

290 ine repertoire at the site of infection with L. major was driven, in part, by pathogen-induced CCL7.

291 lymph node, develop a chronic infection with L. major.

292 ions following an intradermal infection with L. major.

293 UNC93B1 mutant phenotype upon infection with L. major.

294 ent in DM are protected from infections with L. major.

295 , type 1 cytokines than mice inoculated with L. major alone within the first 48 h of infection.

296 d that challenging dysbiotic naive mice with L. major or testing for contact hypersensitivity results

297 ctive immunity, we infected Bim-/- mice with L. major.

298 romoter, and then examined the outcomes with L. major infection.

299 ssed N-Ras short hairpin RNA and pulsed with L. major-expressed MAPK10 enhanced MAPK10-specific Th1-t

300 First, unlike wild-type (WT) L. major, iscl(-) mutants do not trigger polarized T cel