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 language | English (US) |
|---|---|
| Pages (from-to) | 2710-2720 |
| Number of pages | 11 |
| Journal | Journal of Immunology |
| Volume | 201 |
| Issue number | 9 |
| DOIs | |
| State | Published - Nov 1 2018 |
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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 journal › Article
}
TY - JOUR
T1 - Perforin-2 breaches the envelope of phagocytosed bacteria allowing antimicrobial effectors access to intracellular targets
AU - Bai, Fangfang
AU - McCormack, Ryan M.
AU - Hower, Suzanne
AU - Plano, Gregory V
AU - Lichtenheld, Mathias G
AU - Munson, George
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1800365
DO - 10.4049/jimmunol.1800365
M3 - Article
VL - 201
SP - 2710
EP - 2720
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 9
ER -