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Immune reconstitution inflammatory syndrome: the trouble with immunity when you had none

Nature Reviews Microbiology volume 10, pages 150–156 (2012)Cite this article

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Abstract

Some individuals who are infected with HIV rapidly deteriorate shortly after starting antiretroviral therapy, despite effective viral suppression. This reaction, referred to as immune reconstitution inflammatory syndrome (IRIS), is characterized by tissue-destructive inflammation and arises as CD4+ T cells re-emerge. It has been proposed that IRIS is caused by a dysregulation of the expanding population of CD4+ T cells specific for a co-infecting opportunistic pathogen. Here, we argue that IRIS instead results from hyper-responsiveness of the innate immune system to T cell help, a mechanism that may be shared by the many manifestations of IRIS that occur following the reversal of other types of immunosuppression in pathogen-infected hosts.

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Figure 1: Experimental IRIS requires chronic mycobacterial infection of lymphopenic hosts.
Figure 2: Model of IRIS.

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Acknowledgements

The authors thank J. Keane for stimulating discussions during the preparation of this article. Work in the authors' laboratories is supported by the intramural research programme of the US National Institute for Allergy and Infectious Diseases, National Institutes of Health.

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Authors and Affiliations

  1. Daniel L. Barber, Bruno B. Andrade and Alan Sher are at the Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rm 6146, 50 South Drive, Bethesda, Maryland, 20892, USA.,

    Daniel L. Barber, Bruno B. Andrade & Alan Sher

  2. Irini Sereti is at the Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rm 11B07, 10 Center Drive, Bethesda, Maryland 20892, USA.,

    Irini Sereti

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Correspondence to Daniel L. Barber.

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Barber, D., Andrade, B., Sereti, I. et al. Immune reconstitution inflammatory syndrome: the trouble with immunity when you had none. Nat Rev Microbiol 10, 150–156 (2012). https://doi.org/10.1038/nrmicro2712

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