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 Munson

Research output: Contribution to journalArticle

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

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Phagocytosis
Bacteria
Peptide Hydrolases
Salmonella enterica
Phagocytes
perforin 2
Superoxide Dismutase
Virulence
Macrophages
Genes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Perforin-2 breaches the envelope of phagocytosed bacteria allowing antimicrobial effectors access to intracellular targets. / Bai, Fangfang; McCormack, Ryan M.; Hower, Suzanne; Plano, Gregory V; Lichtenheld, Mathias G; Munson, George.

In: Journal of Immunology, Vol. 201, No. 9, 01.11.2018, p. 2710-2720.

Research output: Contribution to journalArticle

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AU - Lichtenheld, Mathias G

AU - Munson, George

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