title: Parasite densities modulate susceptibility of mice to cerebral malaria during co-infection with Schistosoma japonicum and Plasmodium berghei.
abstract: BACKGROUND
  Malaria and schistosomiasis are endemic and co-exist in the same geographic areas, even co-infecting the same host. Previous studies have reported that concomitant infection with Schistosoma japonicum could offer protection against experimental cerebral malaria (ECM) in mice. This study was performed to evaluate whether alterations in parasite density could alter this protective effect.
  
  
  METHODS
  Mice were inoculated with 100 or 200 S. japonicum cercariae followed by infection with high or low density of Plasmodium berghei ANKA strain eight weeks after the first infection. Then, parasitaemia, survival rate and blood-brain-barrier (BBB) damage were assessed. Interferon-gamma (IFN-γ), interleukin (IL)-4, IL-5, IL-13, IL-10, and TGF-β levels were determined in splenocyte supernatants using enzyme-linked immunosorbent assay (ELISA). Cell surface/intracellular staining and flow cytometry were used to analyse the level of CD4(+)/CD8(+) T cells, CD4(+)CD25(+)Foxp3(+) Tregs, IL-10-secreting Tregs, and IL-10(+)Foxp3-CD4(+) T cells in the spleen, and CD4(+)/CD8(+) T cells infiltrating the brain.
  
  
  RESULTS
  Co-infection with low density P. berghei and increased S. japonicum cercariae significantly increased the levels of IL-4, IL-5, IL-13, TGF-β and Tregs, but significantly decreased the levels of IFN-γ and the percentage of CD4(+) T cells and CD8(+) T cells in the spleen and CD8(+) T cell infiltration in the brain. Increased worm loads also significantly decreased mortality and BBB impairment during ECM. When challenged with higher numbers of P. berghei and increased cercariae, the observed cytokine changes were not statistically significant. The corresponding ECM mortality and BBB impairment also remained unchanged.
  
  
  CONCLUSIONS
  This study demonstrates that protection for ECM depends on the numbers of the parasites, S. japonicum and P. berghei, during co-infection. Alterations in the regulatory response appear to play a key role in this adaptation.
authors.forename: Mei-lian
authors.initials: ML
authors.lastname: Wang
authors.forename: Yong-hui
authors.initials: YH
authors.lastname: Feng
authors.forename: Wei
authors.initials: W
authors.lastname: Pang
authors.forename: Zan-mei
authors.initials: ZM
authors.lastname: Qi
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ya-jun
authors.initials: YJ
authors.lastname: Guo
authors.forename: En-jie
authors.initials: EJ
authors.lastname: Luo
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, China Medical University, No 92 Beier Road, Heping District, Shenyang 110001, China. ymcao@mail.cmu.edu.cn.
authors.forename: Ya-ming
authors.initials: YM
authors.lastname: Cao
mesh_terms: D000818:Animals; D060085:Coinfection / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D016779:Malaria, Cerebral / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018512:Parasitemia / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D010962:Plasmodium berghei / Q000276:immunology*; D012549:Schistosoma japonicum / Q000276:immunology*; D012554:Schistosomiasis japonica / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D013154:Spleen / Q000276:immunology
chemical_list: D016207:Cytokines