Understanding Human-Plasmodium falciparum Immune Interactions Uncovers the Immunological Role of Worms |
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Authors: | Christian Roussilhon Philippe Brasseur Patrice Agnamey Jean-Louis Pérignon Pierre Druilhe |
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Institution: | 1. Unité de Parasitologie Bio-Médicale, Institut Pasteur, Paris, France.; 2. UMR 198, Institut de Recherche pour le Développement, Dakar, Sénégal.; 3. Laboratoire de Parasitologie-Mycologie, Hopital Sud, CHU d''Amiens, Amiens, France.;Queensland Institute of Medical Research, Australia |
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Abstract: | BackgroundFormer studies have pointed to a monocyte-dependant 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.Methods and FindingsWe 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.ConclusionThe 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. |
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