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Understanding Mechanisms Underlying the Pathology of Immune Reconstitution Inflammatory Syndrome (IRIS) by Using Animal Models

  • Mycology (M Noverr, Section Editor)
  • Published:
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Abstract

Purpose of Review

Despite the increasing number of clinical reports on immune reconstitution inflammatory syndrome (IRIS), mechanistic understanding of IRIS is still largely limited. The main focus of this review is to summarize animal studies, which were performed to better understand the cellular and molecular mechanisms underlying the pathology of IRIS.

Recent Findings

Three IRIS animal models have been reported. They are mycobacterial IRIS (M-IRIS), cryptococcal IRIS (C-IRIS), and Pneumocystis-IRIS. M-IRIS animal model suggested that, rather than lymphopenia itself, the failure to clear the pathogen by T cells results in excessive priming of the innate immune system. Under the condition, hosts likely suffer IRIS upon T cell reconstitution. Interestingly, T cells specific to self-antigens, not only pathogen-specific, could drive IRIS as well.

Summary

The mechanism to develop IRIS is quite complicated, including multiple layers of host immune responses, the innate immune system that detects pathogens and primes host immunity, and the adaptive immune system that is reconstituted but hyper-activated particularly through CD4+ T cells. Animal models of IRIS, although there are still small numbers of studies available, have already provided significant insights on the mechanistic understanding of IRIS.

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Acknowledgments

Preparation of this article was supported by NIH/NIAID R01-AI088100 and R21-AI135999 awarded to MLS.

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Author notes

  1. Nupur Aggarwal and William Barclay contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology, Duke University School of Medicine, Durham, NC, USA

    Nupur Aggarwal, William Barclay & Mari L. Shinohara

  2. Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA

    Mari L. Shinohara

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  1. Nupur Aggarwal
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  2. William Barclay
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Correspondence to Mari L. Shinohara.

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Nupur Aggarwal, William Barclay, and Mari Shinohara declare that they have no conflicts of interest.

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This is a review article and does not contain any studies with human or animal subjects performed by any of the authors.

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Aggarwal, N., Barclay, W. & Shinohara, M.L. Understanding Mechanisms Underlying the Pathology of Immune Reconstitution Inflammatory Syndrome (IRIS) by Using Animal Models. Curr Clin Micro Rpt 5, 201–209 (2018). https://doi.org/10.1007/s40588-018-0099-5

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