The helminth product ES-62 protects against septic shock via Toll-like receptor 4–dependent autophagosomal degradation of the adaptor MyD88

  • A Retraction to this article was published on 19 July 2011


Sepsis is one of the most challenging health problems worldwide. Here we found that phagocytes from patients with sepsis had considerable upregulation of Toll-like receptor 4 (TLR4) and TLR2; however, shock-inducing inflammatory responses mediated by these TLRs were inhibited by ES-62, an immunomodulator secreted by the filarial nematode Acanthocheilonema viteae. ES-62 subverted TLR4 signaling to block TLR2- and TLR4-driven inflammatory responses via autophagosome-mediated downregulation of the TLR adaptor-transducer MyD88. In vivo, ES-62 protected mice against endotoxic and polymicrobial septic shock by TLR4-mediated induction of autophagy and was protective even when administered after the induction of sepsis. Given that the treatments for septic shock at present are inadequate, the autophagy-dependent mechanism of action by ES-62 might form the basis for urgently needed therapeutic intervention against this life-threatening condition.

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Figure 1: Effects of ES-62 on human macrophages.
Figure 2: Effect of ES-62 on phagocytes from patients with sepsis.
Figure 3: ES-62 targets TLR4 and MyD88 to early and late endosomes.
Figure 4: ES-62 induces autophagosome formation.
Figure 5: ES-62 protects against endotoxic shock.
Figure 6: ES-62 protects against polymicrobial sepsis.
Figure 7: ES-62 protects via autophagy in vivo.
Figure 8: Therapeutic role for ES-62 in polymicrobial sepsis.

Change history

  • 24 June 2011

    The authors wish to note the following. Irregularities have been identified in some of the figures in this paper. The conclusions drawn from these data, that ES-62 protects against the development of pathology in the sepsis models and results in the induction of autophagy in macrophages, cannot be made. As these conclusions constitute major components of the paper, we wish to retract this paper.


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Supported by the Medical Research Council UK (G0700794), the Biomedical Research Council of Singapore, the Wellcome Trust, the Biotechnology and Biological Sciences Research Council UK and the American Asthma Foundation.

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P.P., M.A.M., H.K.T., L.A.-R. and J.R. did experiments; S.M.M. supplied reagents; A.J.M. conceived of the study; A.J.M., M.M.H., S.P. and W.H. planned the experiments, supervised the study and wrote the paper; and all authors analyzed data.

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Correspondence to Alirio J Melendez.

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The authors declare no competing financial interests.

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Puneet, P., McGrath, M., Tay, H. et al. The helminth product ES-62 protects against septic shock via Toll-like receptor 4–dependent autophagosomal degradation of the adaptor MyD88. Nat Immunol 12, 344–351 (2011).

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