IL-33-Mediated Protection against Experimental Cerebral Malaria Is Linked to Induction of Type 2 Innate Lymphoid Cells,M2 Macrophages and Regulatory T Cells

Cerebral malaria (cm) is a complex parasitic disease caused by plasmodium sp. failure to establish an appropriate balance between pro- and anti-inflammatory immune responses is believed to contribute to the development of cerebral pathology. using the blood-stage pba (plasmodium berghei anka) model of infection,we show here that administration of the pro-th2 cytokine,il-33,prevents the development of experimental cerebral malaria (ecm) in c57bl/6 mice and reduces the production of inflammatory mediators ifn-γ,il-12 and tnf-α. il-33 drives the expansion of type-2 innate lymphoid cells (ilc2) that produce type-2 cytokines (il-4,il-5 and il-13),leading to the polarization of the anti-inflammatory m2 macrophages,which in turn expand foxp3 regulatory t cells (tregs). pba-infected mice adoptively transferred with ilc2 have elevated frequency of m2 and tregs and are protected from ecm. importantly,il-33-treated mice deleted of tregs (dereg mice) are no longer able to resist ecm. our data therefore provide evidence that il-33 can prevent the development of ecm by orchestrating a protective immune response via ilc2,m2 macrophages and tregs. © 2015 besnard et al.