title: Loss of Toll-like receptor 7 alters cytokine production and protects against experimental cerebral malaria.
abstract: BACKGROUND
  Malaria, caused by Plasmodium sp. parasites, is a leading cause of global morbidity and mortality. Cerebral malaria, characterized by neurological symptoms, is a life-threatening complication of malaria affecting over 500,000 young children in Africa every year. Because of the prevalence and severity of cerebral malaria, a better understanding of the underlying molecular mechanisms of its pathology is desirable and could inform future development of therapeutics. This study sought to clarify the role of Toll-like receptors (TLRs) in promoting immunopathology associated with cerebral malaria, with a particular focus on the understudied TLR7.
  
  
  METHODS
  Using the Plasmodium berghei ANKA mouse model of experimental cerebral malaria, C57BL/6 mice deficient in various TLRs were infected, and their resistance to cerebral malaria and immune activation through cytokine production were measured.
  
  
  RESULTS
  Loss of TLR7 conferred partial protection against fatal experimental cerebral malaria. Additionally, loss of TLR signalling dysregulated the cytokine profile, resulting in a shift in the cytokine balance towards those with more anti-inflammatory properties.
  
  
  CONCLUSIONS
  This work identifies signalling through TLR7 as a source of pathology in experimental cerebral malaria.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Baccarella
authors.forename: Brian W
authors.initials: BW
authors.lastname: Huang
authors.forename: Mary F
authors.initials: MF
authors.lastname: Fontana
authors.affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA 94143, USA. charlie.kim@ucsf.edu.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Kim
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D060467:Disease Resistance; D016779:Malaria, Cerebral / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010962:Plasmodium berghei / Q000254:growth & development / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000276:immunology*
chemical_list: D016207:Cytokines; D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7