Perforin-2 breaches the envelope of phagocytosed bacteria allowing antimicrobial effectors access to intracellular targets

Fangfang Bai, Ryan M. McCormack, Suzanne Hower, Gregory V. Plano, Mathias G. Lichtenheld, George P. Munson

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Perforin-2, the product of the MPEG1 gene, limits the spread and dissemination of bacterial pathogens in vivo. It is highly expressed in murine and human phagocytes, and macrophages lacking Perforin-2 are compromised in their ability to kill phagocytosed bacteria. In this study, we used Salmonella enterica serovar Typhimurium as a model intracellular pathogen to elucidate the mechanism of Perforin-2's bactericidal activity. In vitro Perforin-2 was found to facilitate the degradation of Ags contained within the envelope of phagocytosed bacteria. In contrast, degradation of a representative surface Ag was found to be independent of Perforin-2. Consistent with our in vitro results, a protease-sensitive, periplasmic superoxide dismutase (SodCII) contributed to the virulence of S. Typhimurium in Perforin-2 knockout but not wild-type mice. In aggregate, our studies indicate that Perforin-2 breaches the envelope of phagocytosed bacteria, facilitating the delivery of proteases and other antimicrobial effectors to sites within the bacterial cell.

Original languageEnglish (US)
Pages (from-to)2710-2720
Number of pages11
JournalJournal of Immunology
Volume201
Issue number9
DOIs
StatePublished - Nov 1 2018

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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