Mrp1 is Involved in Lipid Presentation and INKT Cell Activation by Streptococcus Pneumoniae

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Oct 17

PMID 30323255

Citations 9

Authors

Shilpi Chandra

James Gray

William B Kiosses

Archana Khurana

Kaori Hitomi

Catherine M Crosby

Ashu Chawla

Zheng Fu

Meng Zhao

Natacha Veerapen

Stewart K Richardson

Steven A Porcelli

Gurdyal Besra

Amy R Howell

Sonia Sharma

Bjoern Peters

Mitchell Kronenberg

Affiliations

Soon will be listed here.

Abstract

Invariant natural killer T cells (iNKT cells) are activated by lipid antigens presented by CD1d, but the pathway leading to lipid antigen presentation remains incompletely characterized. Here we show a whole-genome siRNA screen to elucidate the CD1d presentation pathway. A majority of gene knockdowns that diminish antigen presentation reduced formation of glycolipid-CD1d complexes on the cell surface, including members of the HOPS and ESCRT complexes, genes affecting cytoskeletal rearrangement, and ABC family transporters. We validated the role in vivo for the multidrug resistance protein 1 (Mrp1) in CD1d antigen presentation. Mrp1 deficiency reduces surface clustering of CD1d, which decreased iNKT cell activation. Infected Mrp1 knockout mice show decreased iNKT cell responses to antigens from Streptococcus pneumoniae and were associated with increased mortality. Our results highlight the unique cellular events involved in lipid antigen presentation and show how modification of this pathway can lead to lethal infection.

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