PXD039804-1

PXD039804 is an original dataset announced via ProteomeXchange.

Title	Translatome analyses by bio-orthogonal non-canonical amino acid labeling reveal that MR1-activated MAIT cells induce an M1 phenotype and antiviral programming in antigen-presenting monocytes_bicellular2
Description	MAIT cells are multifunctional innate-like effector cells recognizing bacterial-derived vitamin B metabolites presented by the non-polymorphic MHC class I related-1 molecule (MR1). Activated MAIT cells can exert regulatory, pro-inflammatory, or cytotoxic responses that enable the direct killing of infected cells. While tremendous progress regarding the multifaceted roles of MAIT cells has been made in the last decade, our understanding of the MR1-mediated responses of MAIT cells upon their interaction with other immune cells is still incomplete. Here, we performed the first translatome study of primary human MAIT cells interacting with THP-1 monocytes in a bicellular system. We analyzed the interaction between MAIT and THP-1 cells in the presence of the activating 5-OP-RU or the inhibitory Ac-6-FP MR1-ligand. Using bio-orthogonal non-canonical amino acid tagging (BONCAT) we were able to enrich selectively those proteins that were newly translated during MR1-dependent cellular interaction. Subsequently, newly translated proteins were measured cell-type-specifically by ultrasensitive proteomics to decipher the coinciding immune responses in both cell types. This strategy identified over 2,000 MAIT and 3,000 THP-1 active protein translations following MR-1 ligand stimulations. Translation of both cell types was more efficiently induced by 5-OP-RU in comparison to Ac-6-FP, which correlated with higher conjugation frequencies and CD3 polarization at immunological synapses. In addition to known effector responses, protein translations uncovered type I and type II Interferon-driven protein expression profiles in both 5-OP-RU-stimulated MAIT and THP-1 cells. Interestingly, the translatome of THP-1 macrophages suggested that activated MAIT cells can impact M1/M2 polarization in these cells. Indeed, gene and surface expression of CXCL10, IL-1, CD80, and CD206 confirmed an M1-like phenotype of macrophages being induced in the presence of 5-OP-RU-activated MAIT cells. Furthermore, we validated that the Interferon-driven translatome was accompanied by the induction of an antiviral phenotype in THP-1 cells, which were found able to suppress viral replication following conjugation with MR1-activated MAIT cells. In conclusion, BONCAT translatomics extended our knowledge of MAIT cell immune responses at the protein level and discovered that MR1-activated MAIT cells are sufficient to induce M1 polarization and an anti-viral program of macrophages.
HostingRepository	PRIDE
AnnounceDate	2023-02-08
AnnouncementXML	Submission_2023-02-08_04:15:26.039.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	LotharJaensch
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-02 08:31:30	ID requested
⏵ 1	2023-02-08 04:15:26	announced
2	2023-11-14 09:00:24	announced	2023-11-14: Updated project metadata.

submitter keyword: BONCAT,MAIT cell, antiviral, Translatome, MR1-mediated MAIT cell activation, M1 macrophage polarization, Proteomics

LotharJaensch
contact affiliation	Cellular Proteomics, Helmholtz Centre for Infection Research, Braunschweig, Germany
contact email	lothar.jaensch@helmholtz-hzi.de
lab head
LotharJaensch
contact affiliation	HZI
contact email	Lothar.Jaensch@Helmholtz-HZI.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD039804
     1. Label: PRIDE project
     2. Name: Translatome analyses by bio-orthogonal non-canonical amino acid labeling reveal that MR1-activated MAIT cells induce an M1 phenotype and antiviral programming in antigen-presenting monocytes_bicellular2