TLR signals induce phagosomal MHC-I delivery from the endosomal recycling compartment to allow cross-presentation

Priyanka Nair-Gupta; Alessia Baccarini; Navpreet Tung; Fabian Seyffer; Oliver Florey; Yunjie Huang; Meenakshi Banerjee; Michael Overholtzer; Paul A. Roche; Robert Tampé; Brian D. Brown; Derk Amsen; Sidney W. Whiteheart; J. Magarian Blander

doi:10.1016/j.cell.2014.04.054

TLR signals induce phagosomal MHC-I delivery from the endosomal recycling compartment to allow cross-presentation

Priyanka Nair-Gupta, Alessia Baccarini, Navpreet Tung, Fabian Seyffer, Oliver Florey, Yunjie Huang, Meenakshi Banerjee, Michael Overholtzer, Paul A. Roche, Robert Tampé, Brian D. Brown, Derk Amsen, Sidney W. Whiteheart, J. Magarian Blander

Molecular and Cellular Biochemistry

Research output: Contribution to journal › Article › peer-review

278 Scopus citations

Abstract

Adaptation of the endoplasmic reticulum (ER) pathway for MHC class I (MHC-I) presentation in dendritic cells enables cross-presentation of peptides derived from phagocytosed microbes, infected cells, or tumor cells to CD8 T cells. How these peptides intersect with MHC-I molecules remains poorly understood. Here, we show that MHC-I selectively accumulate within phagosomes carrying microbial components, which engage Toll-like receptor (TLR) signaling. Although cross-presentation requires Sec22b-mediated phagosomal recruitment of the peptide loading complex from the ER-Golgi intermediate compartment (ERGIC), this step is independent of TLR signaling and does not deliver MHC-I. Instead, MHC-I are recruited from an endosomal recycling compartment (ERC), which is marked by Rab11a, VAMP3/cellubrevin, and VAMP8/endobrevin and holds large reserves of MHC-I. While Rab11a activity stocks ERC stores with MHC-I, MyD88-dependent TLR signals drive IκB-kinase (IKK)2-mediated phosphorylation of phagosome-associated SNAP23. Phospho-SNAP23 stabilizes SNARE complexes orchestrating ERC-phagosome fusion, enrichment of phagosomes with ERC-derived MHC-I, and subsequent cross-presentation during infection. PaperFlick

Original language	English
Pages (from-to)	506-521
Number of pages	16
Journal	Cell
Volume	158
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2014.04.054
State	Published - Jul 31 2014

Bibliographical note

Funding Information:
We thank E.S. Trombetta, T. Moran, A. Garcia-Sastre, C. Harding, R. Germain, N. Aronin, M.M. DiFiglia, I. Verma, K. Suzuki, and S. Amigorena for reagents. We are grateful to E. Kavalali, B. Trinité, F. Gebhardt, H. Pêche, current J.M.B. laboratory members, H. Gupta, M. Blander, and S.J. Blander for technical assistance, discussions, and support. ISMMS-Microscopy Shared Resource Facility was supported by NIH grants 5R24 CA095823-04, S10 RR0 9145-01, and NSF DBI-9724504. This work was supported by NIH grants AI073899 to J.M.B., HL56652 and HL082193 to S.W.W., AI104848 to B.D.B., CA154649 to M.O., German Research Foundation grants SFB 807–Membrane Transport and Communication and TA157/7 to R.T., and grants from the Landsteiner Foundation for Blood Research and The Dutch Organization for Science to D.A. J.M.B. is supported by NIH grants DK072201 and AI095245, the Burroughs Wellcome Fund, and American Cancer Society grant 117254.

Funding

We thank E.S. Trombetta, T. Moran, A. Garcia-Sastre, C. Harding, R. Germain, N. Aronin, M.M. DiFiglia, I. Verma, K. Suzuki, and S. Amigorena for reagents. We are grateful to E. Kavalali, B. Trinit\u00E9, F. Gebhardt, H. P\u00EAche, current J.M.B. laboratory members, H. Gupta, M. Blander, and S.J. Blander for technical assistance, discussions, and support. ISMMS-Microscopy Shared Resource Facility was supported by NIH grants 5R24 CA095823-04, S10 RR0 9145-01, and NSF DBI-9724504. This work was supported by NIH grants AI073899 to J.M.B., HL56652 and HL082193 to S.W.W., AI104848 to B.D.B., CA154649 to M.O., German Research Foundation grants SFB 807\u2013Membrane Transport and Communication and TA157/7 to R.T., and grants from the Landsteiner Foundation for Blood Research and The Dutch Organization for Science to D.A. J.M.B. is supported by NIH grants DK072201 and AI095245, the Burroughs Wellcome Fund, and American Cancer Society grant 117254.

Funders	Funder number
Landsteiner Foundation for Blood Research
Burroughs Wellcome Fund
Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases	R01AI095245, R56AI073899, R01AI104848
National Childhood Cancer Registry – National Cancer Institute	R24CA095823, R01CA154649, ZIABC011035
Dutch Organization for Science	DK072201, AI095245
U.S. Department of Energy Chinese Academy of Sciences Guangzhou Municipal Science and Technology Project Oak Ridge National Laboratory Extreme Science and Engineering Discovery Environment National Science Foundation National Energy Research Scientific Computing Center National Natural Science Foundation of China	HL082193, AI073899, 9724504
National Heart, Lung, and Blood Institute Family Blood Pressure Program	R01HL091893, R01HL056652
American Cancer Society-Michigan Cancer Research Fund	117254
National Center for Research Resources	S10RR009145
Deutsche Forschungsgemeinschaft	SFB 807, TA157/7
National Institutes of Health (NIH)	S10 RR0 9145-01
National Institute of Diabetes and Digestive and Kidney Diseases	P01DK072201

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2014.04.054

Cite this

Nair-Gupta, P., Baccarini, A., Tung, N., Seyffer, F., Florey, O., Huang, Y., Banerjee, M., Overholtzer, M., Roche, P. A., Tampé, R., Brown, B. D., Amsen, D., Whiteheart, S. W., & Blander, J. M. (2014). TLR signals induce phagosomal MHC-I delivery from the endosomal recycling compartment to allow cross-presentation. Cell, 158(3), 506-521. https://doi.org/10.1016/j.cell.2014.04.054

@article{10cfba44d3de4e198fc8e95fef43a8cc,

title = "TLR signals induce phagosomal MHC-I delivery from the endosomal recycling compartment to allow cross-presentation",

abstract = "Adaptation of the endoplasmic reticulum (ER) pathway for MHC class I (MHC-I) presentation in dendritic cells enables cross-presentation of peptides derived from phagocytosed microbes, infected cells, or tumor cells to CD8 T cells. How these peptides intersect with MHC-I molecules remains poorly understood. Here, we show that MHC-I selectively accumulate within phagosomes carrying microbial components, which engage Toll-like receptor (TLR) signaling. Although cross-presentation requires Sec22b-mediated phagosomal recruitment of the peptide loading complex from the ER-Golgi intermediate compartment (ERGIC), this step is independent of TLR signaling and does not deliver MHC-I. Instead, MHC-I are recruited from an endosomal recycling compartment (ERC), which is marked by Rab11a, VAMP3/cellubrevin, and VAMP8/endobrevin and holds large reserves of MHC-I. While Rab11a activity stocks ERC stores with MHC-I, MyD88-dependent TLR signals drive IκB-kinase (IKK)2-mediated phosphorylation of phagosome-associated SNAP23. Phospho-SNAP23 stabilizes SNARE complexes orchestrating ERC-phagosome fusion, enrichment of phagosomes with ERC-derived MHC-I, and subsequent cross-presentation during infection. PaperFlick",

author = "Priyanka Nair-Gupta and Alessia Baccarini and Navpreet Tung and Fabian Seyffer and Oliver Florey and Yunjie Huang and Meenakshi Banerjee and Michael Overholtzer and Roche, \{Paul A.\} and Robert Tamp{\'e} and Brown, \{Brian D.\} and Derk Amsen and Whiteheart, \{Sidney W.\} and Blander, \{J. Magarian\}",

note = "Funding Information: We thank E.S. Trombetta, T. Moran, A. Garcia-Sastre, C. Harding, R. Germain, N. Aronin, M.M. DiFiglia, I. Verma, K. Suzuki, and S. Amigorena for reagents. We are grateful to E. Kavalali, B. Trinit{\'e}, F. Gebhardt, H. P{\^e}che, current J.M.B. laboratory members, H. Gupta, M. Blander, and S.J. Blander for technical assistance, discussions, and support. ISMMS-Microscopy Shared Resource Facility was supported by NIH grants 5R24 CA095823-04, S10 RR0 9145-01, and NSF DBI-9724504. This work was supported by NIH grants AI073899 to J.M.B., HL56652 and HL082193 to S.W.W., AI104848 to B.D.B., CA154649 to M.O., German Research Foundation grants SFB 807–Membrane Transport and Communication and TA157/7 to R.T., and grants from the Landsteiner Foundation for Blood Research and The Dutch Organization for Science to D.A. J.M.B. is supported by NIH grants DK072201 and AI095245, the Burroughs Wellcome Fund, and American Cancer Society grant 117254. ",

year = "2014",

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doi = "10.1016/j.cell.2014.04.054",

language = "English",

volume = "158",

pages = "506--521",

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Nair-Gupta, P, Baccarini, A, Tung, N, Seyffer, F, Florey, O, Huang, Y, Banerjee, M, Overholtzer, M, Roche, PA, Tampé, R, Brown, BD, Amsen, D, Whiteheart, SW & Blander, JM 2014, 'TLR signals induce phagosomal MHC-I delivery from the endosomal recycling compartment to allow cross-presentation', Cell, vol. 158, no. 3, pp. 506-521. https://doi.org/10.1016/j.cell.2014.04.054

TY - JOUR

T1 - TLR signals induce phagosomal MHC-I delivery from the endosomal recycling compartment to allow cross-presentation

AU - Nair-Gupta, Priyanka

AU - Baccarini, Alessia

AU - Tung, Navpreet

AU - Seyffer, Fabian

AU - Florey, Oliver

AU - Huang, Yunjie

AU - Banerjee, Meenakshi

AU - Overholtzer, Michael

AU - Roche, Paul A.

AU - Tampé, Robert

AU - Brown, Brian D.

AU - Amsen, Derk

AU - Whiteheart, Sidney W.

AU - Blander, J. Magarian

N1 - Funding Information: We thank E.S. Trombetta, T. Moran, A. Garcia-Sastre, C. Harding, R. Germain, N. Aronin, M.M. DiFiglia, I. Verma, K. Suzuki, and S. Amigorena for reagents. We are grateful to E. Kavalali, B. Trinité, F. Gebhardt, H. Pêche, current J.M.B. laboratory members, H. Gupta, M. Blander, and S.J. Blander for technical assistance, discussions, and support. ISMMS-Microscopy Shared Resource Facility was supported by NIH grants 5R24 CA095823-04, S10 RR0 9145-01, and NSF DBI-9724504. This work was supported by NIH grants AI073899 to J.M.B., HL56652 and HL082193 to S.W.W., AI104848 to B.D.B., CA154649 to M.O., German Research Foundation grants SFB 807–Membrane Transport and Communication and TA157/7 to R.T., and grants from the Landsteiner Foundation for Blood Research and The Dutch Organization for Science to D.A. J.M.B. is supported by NIH grants DK072201 and AI095245, the Burroughs Wellcome Fund, and American Cancer Society grant 117254.

PY - 2014/7/31

Y1 - 2014/7/31

N2 - Adaptation of the endoplasmic reticulum (ER) pathway for MHC class I (MHC-I) presentation in dendritic cells enables cross-presentation of peptides derived from phagocytosed microbes, infected cells, or tumor cells to CD8 T cells. How these peptides intersect with MHC-I molecules remains poorly understood. Here, we show that MHC-I selectively accumulate within phagosomes carrying microbial components, which engage Toll-like receptor (TLR) signaling. Although cross-presentation requires Sec22b-mediated phagosomal recruitment of the peptide loading complex from the ER-Golgi intermediate compartment (ERGIC), this step is independent of TLR signaling and does not deliver MHC-I. Instead, MHC-I are recruited from an endosomal recycling compartment (ERC), which is marked by Rab11a, VAMP3/cellubrevin, and VAMP8/endobrevin and holds large reserves of MHC-I. While Rab11a activity stocks ERC stores with MHC-I, MyD88-dependent TLR signals drive IκB-kinase (IKK)2-mediated phosphorylation of phagosome-associated SNAP23. Phospho-SNAP23 stabilizes SNARE complexes orchestrating ERC-phagosome fusion, enrichment of phagosomes with ERC-derived MHC-I, and subsequent cross-presentation during infection. PaperFlick

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TLR signals induce phagosomal MHC-I delivery from the endosomal recycling compartment to allow cross-presentation

Abstract

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