title: Plasmodium yoelii blood-stage primes macrophage-mediated innate immune response through modulation of toll-like receptor signalling.
abstract: BACKGROUND
  Toll-like receptors (TLRs) signalling is reported to be primed by the infection of human malaria parasite, Plasmodium falciparum. However, little is known about the regulation of macrophages TLR signalling by the infection of lethal or non-lethal strain of rodent malaria parasites.
  
  
  METHODS
  BALB/c mice were infected with non-lethal strain Plasmodium yoelii 17XNL or lethal strain P. yoelii 17XL. Peritoneal macrophages were isolated to study its immune response to pRBC lysate, and TLRs (TLR2, TLR4, and TLR9) agonists, and the expression of TLRs and intracellular signalling molecules were also investigated by flow cytometry and semi-quantitive RT-PCR.
  
  
  RESULTS
  The reactivity of peritoneal macrophages from the mice infected with lethal strain P. y 17XL or non-lethal strain P. y 17XNL were enhanced to pRBC lysate, and TLR2, TLR4, and TLR9 agonists at one, three and five days post-infection. Of all the tested TLRs, only TLR2 was up-regulated on peritoneal macrophages of mice infected with either strain. However, transcription of intracellular signalling molecules MyD88, IRAK-1, and TRAF-6 was significantly up-regulated in peritoneal macrophages from mice infected either with P. yoelii 17XL or P. yoelii 17XNL at one, three and five days post-infection. However, the enhanced TLRs response of macrophage from P. yoelii 17XNL-infected mice persisted for a much longer time than that from P. yoelii 17XL-infected mice.
  
  
  CONCLUSIONS
  Both P. yoelii 17XL and 17XNL strains could enhance the response of peritoneal macrophages to pRBC lysate and TLR agonists, through up-regulating the expression of TLR2 and intracellular signalling molecules MyD88, IRAK-1, and TRAF-6. In addition, prolonged high response of macrophage from P. yoelii 17XNL-infected mice might be associated with the more efficiently controlling of P. yoelii 17XNL growth in mice at early stage.
authors.affiliation: Department of Pathogenic Biology, Third Military Medical University, 30 Gaotanyan Zhengjie, Shapingba District, Chongqing 400038, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Fu
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.forename: Taoli
authors.initials: T
authors.lastname: Zhou
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Fu
authors.forename: Wenyue
authors.initials: W
authors.lastname: Xu
mesh_terms: D000818:Animals; D002457:Cell Extracts / Q000494:pharmacology; D002478:Cells, Cultured; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D007113:Immunity, Innate / Q000187:drug effects; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000276:immunology; D055666:Lipopeptides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology*; D008288:Malaria / Q000276:immunology / Q000469:parasitology / Q000662:veterinary; D051379:Mice; D008807:Mice, Inbred BALB C; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology; D010967:Plasmodium yoelii / Q000276:immunology*; D012376:Rodent Diseases / Q000276:immunology* / Q000469:parasitology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000276:immunology; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology*
chemical_list: D002457:Cell Extracts; D055666:Lipopeptides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D048029:TNF Receptor-Associated Factor 6; D051193:Toll-Like Receptors; D053592:Interleukin-1 Receptor-Associated Kinases; C507769:Irak1 protein, mouse