1921
Volume 83, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

Severe malaria represents a clinical spectrum of disease. We propose that innate immune inflammatory responses to malaria play key roles in the pathogenesis and clinical outcomes of distinct severe malaria syndromes. To investigate this hypothesis, mice deficient in IRAK4, central to Toll-like receptor (TLR)-mediated signaling, were studied in two experimental models of malaria: (PbA) and (PccAS). mice had decreased pro-inflammatory cytokine production during infection in both models. However, animals were relatively protected from PbA-associated symptoms compared with wild-type mice, whereas animals were more susceptible to PccASassociated disease. These results show that IRAK4-mediated innate immune inflammatory responses play critical roles in divergent clinical outcomes in murine malaria models. As such, integrated approaches, using more than one model, are required to fully understand the parasite/host interactions that characterize severe malaria, and more importantly, to fully assess the effect of adjunctive therapies targeting innate immune responses to malaria.

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Supplementary Table

  • Received : 13 Dec 2009
  • Accepted : 12 Mar 2010
  • Published online : 06 Jul 2010

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