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McCormack RM, Szymanski EP, Hsu AP, et al. MPEG1/perforin-2 mutations in human pulmonary nontuberculous mycobacterial infections. JCI Insight. 2017;2(8)doi: 10.1172/jci.insight.89635.
McCormack, R. M., Szymanski, E. P., Hsu, A. P., Perez, E., Olivier, K. N., Fisher, E., Goodhew, E. B., Podack, E. R., & Holland, S. M. (2017). MPEG1/perforin-2 mutations in human pulmonary nontuberculous mycobacterial infections. JCI insight, 2(8), . https://doi.org/10.1172/jci.insight.89635
McCormack, Ryan M, et al. "MPEG1/perforin-2 mutations in human pulmonary nontuberculous mycobacterial infections." JCI insight vol. 2,8 (2017). doi: https://doi.org/10.1172/jci.insight.89635
McCormack RM, Szymanski EP, Hsu AP, Perez E, Olivier KN, Fisher E, Goodhew EB, Podack ER, Holland SM. MPEG1/perforin-2 mutations in human pulmonary nontuberculous mycobacterial infections. JCI Insight. 2017 Apr 20;2(8). doi: 10.1172/jci.insight.89635. eCollection 2017 Apr 20. PMID: 28422754; PMCID: PMC5396519.
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JCI Insight. 2017 Apr 20;2(8). doi: 10.1172/jci.insight.89635. eCollection 2017 Apr 20.

MPEG1/perforin-2 mutations in human pulmonary nontuberculous mycobacterial infections.

JCI insight

Ryan M McCormack, Eva P Szymanski, Amy P Hsu, Elena Perez, Kenneth N Olivier, Eva Fisher, E Brook Goodhew, Eckhard R Podack, Steven M Holland

Affiliations

  1. Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida, USA.
  2. Laboratory of Clinical Infectious Diseases, NIAID, NIH.
  3. Cardiovascular and Pulmonary Branch, NHLBI, NIH, Bethesda, Maryland, USA.

PMID: 28422754 PMCID: PMC5396519 DOI: 10.1172/jci.insight.89635

Abstract

Perforin-2 is a highly conserved pore-forming protein encoded by macrophage expressed gene 1 (MPEG1). A number of studies have shown that Perforin-2-deficient mice are unable to survive following a bacterial challenge that is nonlethal in WT mice. There is also recent evidence that Mpeg1+/- heterozygous mice display an intermediate killing ability compared with Mpeg1 WT and Mpeg1-/- mice. Despite these in vivo findings, to date, no perforin-2 deficiencies have been associated with human disease. Here, we report four patients with persistent nontuberculous mycobacterial infection who had heterozygous MPEG1 mutations. In vitro, neutrophils, macrophages, and B cells from these patients were unable to kill Mycobacterium avium as efficiently as normal controls. CRISPR mutagenesis validated the deleterious antibacterial activity of these mutations. These data suggest that perforin-2 haploinsufficiency may contribute to human susceptibility to infections with intracellular bacteria.

Keywords: Genetics; Infectious disease

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