Alternative endogenous protein processing via an autophagy-dependent pathway compensates for Yersinia-mediated inhibition of endosomal major histocompatibility complex class II antigen presentation

Holger Rüssmann, Klaus Panthel, Brigitte Köhn, Stefan Jellbauer, Sebastian E. Winter, Sara Garbom, Hans Wolf-Watz, Sigrid Hoffmann, Silke Grauling-Halama, Gernot Geginat

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Extracellular Yersinia pseudotuberculosis employs a type III secretion system (T3SS) for translocating virulence factors (Yersinia outer proteins [Yops]) directly into the cytosol of eukaryotic cells. Recently, we used YopE as a carrier molecule for T3SS-dependent secretion and translocation of listeriolysin O (LLO) from Listeria monocytogenes. We demonstrated that translocation of chimeric YopE/LLO into the cytosol of macrophages by Yersinia results in the induction of a codominant antigen-specific CD4 and CD8 T-cell response in orally immunized mice. In this study, we addressed the requirements for processing and major histocompatibility complex (MHC) class II presentation of chimeric YopE proteins translocated into the cytosol of macrophages by the Yersinia T3SS. Our data demonstrate the ability of Yersinia to counteract exogenous MHC class II antigen presentation of secreted hybrid YopE by the action of wild-type YopE and YopH. In the absence of exogenous MHC class II antigen presentation, an alternative pathway was identified for YopE fusion proteins originating in the cytosol. This endogenous antigen-processing pathway was sensitive to inhibitors of phagolysosomal acidification and macroautophagy, but it did not require the function either of the proteasome or of transporters associated with antigen processing. Thus, by an autophagy-dependent mechanism, macrophages are able to compensate for the YopE/YopH-mediated inhibition of the endosomal MHC class II antigen presentation pathway for exogenous antigens. This is the first report demonstrating that autophagy might enable the host to mount an MHC class II-restricted CD4 T-cell response against translocated bacterial virulence factors. We provide critical new insights into the interaction between the mammalian immune system and a human pathogen.

Original languageEnglish (US)
Pages (from-to)5138-5150
Number of pages13
JournalInfection and Immunity
Volume78
Issue number12
DOIs
StatePublished - Dec 2010

Fingerprint

Yersinia
Histocompatibility Antigens Class II
Autophagy
Antigen Presentation
Major Histocompatibility Complex
Cytosol
Macrophages
Virulence Factors
Proteins
Yersinia pseudotuberculosis
CD8 Antigens
T-Lymphocytes
CD4 Antigens
Listeria monocytogenes
Eukaryotic Cells
Proteasome Endopeptidase Complex
Immune System
Antigens

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Alternative endogenous protein processing via an autophagy-dependent pathway compensates for Yersinia-mediated inhibition of endosomal major histocompatibility complex class II antigen presentation. / Rüssmann, Holger; Panthel, Klaus; Köhn, Brigitte; Jellbauer, Stefan; Winter, Sebastian E.; Garbom, Sara; Wolf-Watz, Hans; Hoffmann, Sigrid; Grauling-Halama, Silke; Geginat, Gernot.

In: Infection and Immunity, Vol. 78, No. 12, 12.2010, p. 5138-5150.

Research output: Contribution to journalArticle

Rüssmann, Holger ; Panthel, Klaus ; Köhn, Brigitte ; Jellbauer, Stefan ; Winter, Sebastian E. ; Garbom, Sara ; Wolf-Watz, Hans ; Hoffmann, Sigrid ; Grauling-Halama, Silke ; Geginat, Gernot. / Alternative endogenous protein processing via an autophagy-dependent pathway compensates for Yersinia-mediated inhibition of endosomal major histocompatibility complex class II antigen presentation. In: Infection and Immunity. 2010 ; Vol. 78, No. 12. pp. 5138-5150.
@article{8060b8759c824d169c352800bd8b5809,
title = "Alternative endogenous protein processing via an autophagy-dependent pathway compensates for Yersinia-mediated inhibition of endosomal major histocompatibility complex class II antigen presentation",
abstract = "Extracellular Yersinia pseudotuberculosis employs a type III secretion system (T3SS) for translocating virulence factors (Yersinia outer proteins [Yops]) directly into the cytosol of eukaryotic cells. Recently, we used YopE as a carrier molecule for T3SS-dependent secretion and translocation of listeriolysin O (LLO) from Listeria monocytogenes. We demonstrated that translocation of chimeric YopE/LLO into the cytosol of macrophages by Yersinia results in the induction of a codominant antigen-specific CD4 and CD8 T-cell response in orally immunized mice. In this study, we addressed the requirements for processing and major histocompatibility complex (MHC) class II presentation of chimeric YopE proteins translocated into the cytosol of macrophages by the Yersinia T3SS. Our data demonstrate the ability of Yersinia to counteract exogenous MHC class II antigen presentation of secreted hybrid YopE by the action of wild-type YopE and YopH. In the absence of exogenous MHC class II antigen presentation, an alternative pathway was identified for YopE fusion proteins originating in the cytosol. This endogenous antigen-processing pathway was sensitive to inhibitors of phagolysosomal acidification and macroautophagy, but it did not require the function either of the proteasome or of transporters associated with antigen processing. Thus, by an autophagy-dependent mechanism, macrophages are able to compensate for the YopE/YopH-mediated inhibition of the endosomal MHC class II antigen presentation pathway for exogenous antigens. This is the first report demonstrating that autophagy might enable the host to mount an MHC class II-restricted CD4 T-cell response against translocated bacterial virulence factors. We provide critical new insights into the interaction between the mammalian immune system and a human pathogen.",
author = "Holger R{\"u}ssmann and Klaus Panthel and Brigitte K{\"o}hn and Stefan Jellbauer and Winter, {Sebastian E.} and Sara Garbom and Hans Wolf-Watz and Sigrid Hoffmann and Silke Grauling-Halama and Gernot Geginat",
year = "2010",
month = "12",
doi = "10.1128/IAI.00155-10",
language = "English (US)",
volume = "78",
pages = "5138--5150",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "12",

}

TY - JOUR

T1 - Alternative endogenous protein processing via an autophagy-dependent pathway compensates for Yersinia-mediated inhibition of endosomal major histocompatibility complex class II antigen presentation

AU - Rüssmann, Holger

AU - Panthel, Klaus

AU - Köhn, Brigitte

AU - Jellbauer, Stefan

AU - Winter, Sebastian E.

AU - Garbom, Sara

AU - Wolf-Watz, Hans

AU - Hoffmann, Sigrid

AU - Grauling-Halama, Silke

AU - Geginat, Gernot

PY - 2010/12

Y1 - 2010/12

N2 - Extracellular Yersinia pseudotuberculosis employs a type III secretion system (T3SS) for translocating virulence factors (Yersinia outer proteins [Yops]) directly into the cytosol of eukaryotic cells. Recently, we used YopE as a carrier molecule for T3SS-dependent secretion and translocation of listeriolysin O (LLO) from Listeria monocytogenes. We demonstrated that translocation of chimeric YopE/LLO into the cytosol of macrophages by Yersinia results in the induction of a codominant antigen-specific CD4 and CD8 T-cell response in orally immunized mice. In this study, we addressed the requirements for processing and major histocompatibility complex (MHC) class II presentation of chimeric YopE proteins translocated into the cytosol of macrophages by the Yersinia T3SS. Our data demonstrate the ability of Yersinia to counteract exogenous MHC class II antigen presentation of secreted hybrid YopE by the action of wild-type YopE and YopH. In the absence of exogenous MHC class II antigen presentation, an alternative pathway was identified for YopE fusion proteins originating in the cytosol. This endogenous antigen-processing pathway was sensitive to inhibitors of phagolysosomal acidification and macroautophagy, but it did not require the function either of the proteasome or of transporters associated with antigen processing. Thus, by an autophagy-dependent mechanism, macrophages are able to compensate for the YopE/YopH-mediated inhibition of the endosomal MHC class II antigen presentation pathway for exogenous antigens. This is the first report demonstrating that autophagy might enable the host to mount an MHC class II-restricted CD4 T-cell response against translocated bacterial virulence factors. We provide critical new insights into the interaction between the mammalian immune system and a human pathogen.

AB - Extracellular Yersinia pseudotuberculosis employs a type III secretion system (T3SS) for translocating virulence factors (Yersinia outer proteins [Yops]) directly into the cytosol of eukaryotic cells. Recently, we used YopE as a carrier molecule for T3SS-dependent secretion and translocation of listeriolysin O (LLO) from Listeria monocytogenes. We demonstrated that translocation of chimeric YopE/LLO into the cytosol of macrophages by Yersinia results in the induction of a codominant antigen-specific CD4 and CD8 T-cell response in orally immunized mice. In this study, we addressed the requirements for processing and major histocompatibility complex (MHC) class II presentation of chimeric YopE proteins translocated into the cytosol of macrophages by the Yersinia T3SS. Our data demonstrate the ability of Yersinia to counteract exogenous MHC class II antigen presentation of secreted hybrid YopE by the action of wild-type YopE and YopH. In the absence of exogenous MHC class II antigen presentation, an alternative pathway was identified for YopE fusion proteins originating in the cytosol. This endogenous antigen-processing pathway was sensitive to inhibitors of phagolysosomal acidification and macroautophagy, but it did not require the function either of the proteasome or of transporters associated with antigen processing. Thus, by an autophagy-dependent mechanism, macrophages are able to compensate for the YopE/YopH-mediated inhibition of the endosomal MHC class II antigen presentation pathway for exogenous antigens. This is the first report demonstrating that autophagy might enable the host to mount an MHC class II-restricted CD4 T-cell response against translocated bacterial virulence factors. We provide critical new insights into the interaction between the mammalian immune system and a human pathogen.

UR - http://www.scopus.com/inward/record.url?scp=78649956093&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78649956093&partnerID=8YFLogxK

U2 - 10.1128/IAI.00155-10

DO - 10.1128/IAI.00155-10

M3 - Article

VL - 78

SP - 5138

EP - 5150

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 12

ER -