title: Understanding human-Plasmodium falciparum immune interactions uncovers the immunological role of worms.
abstract: BACKGROUND
  Former studies have pointed to a monocyte-dependent effect of antibodies in protection against malaria and thereby to cytophilic antibodies IgG1 and IgG3, which trigger monocyte receptors. Field investigations have further documented that a switch from non-cytophilic to cytophilic classes of antimalarial antibodies was associated with protection. The hypothesis that the non-cytophilic isotype imbalance could be related to concomittant helminthic infections was supported by several interventions and case-control studies.
  
  
  RESULTS
  We investigated here the hypothesis that the delayed acquisition of immunity to malaria could be related to a worm-induced Th2 drive on antimalarial immune responses. IgG1 to IgG4 responses against 6 different parasite-derived antigens were analyzed in sera from 203 Senegalese children, half carrying intestinal worms, presenting 421 clinical malaria attacks over 51 months. Results show a significant correlation between the occurrence of malaria attacks, worm carriage (particularly that of hookworms) and a decrease in cytophilic IgG1 and IgG3 responses and an increase in non-cytophilic IgG4 response to the merozoite stage protein 3 (MSP3) vaccine candidate.
  
  
  CONCLUSIONS
  The results confirm the association with protection of anti-MSP3 cytophilic responses, confirm in one additional setting that worms increase malaria morbidity and show a Th2 worm-driven pattern of anti-malarial immune responses. They document why large anthelminthic mass treatments may be worth being assessed as malaria control policies.
authors.affiliation: Unité de Parasitologie Bio-Médicale, Institut Pasteur, Paris, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Roussilhon
authors.forename: Philippe
authors.initials: P
authors.lastname: Brasseur
authors.forename: Patrice
authors.initials: P
authors.lastname: Agnamey
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Pérignon
authors.forename: Pierre
authors.initials: P
authors.lastname: Druilhe
mesh_terms: D000293:Adolescent; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D005260:Female; D006373:Helminthiasis / Q000453:epidemiology / Q000276:immunology*; D006376:Helminths / Q000276:immunology* / Q000502:physiology; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007223:Infant; D016778:Malaria, Falciparum / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology* / Q000502:physiology; D011446:Prospective Studies; D015800:Protozoan Proteins / Q000276:immunology; D012675:Senegal / Q000453:epidemiology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D015800:Protozoan Proteins; C089133:merozoite surface protein 3, Plasmodium