CXCL16 Stimulates Antigen-Induced MAIT Cell Accumulation but Trafficking During Lung Infection Is CXCR6-Independent.

Huifeng Yu,David P Fairlie,Ligong Liu,Jeffrey Y W Mak,Siobhan Cowley,Amy Yang

doi:10.3389/fimmu.2020.01773

Abstract

Mucosa-associated invariant T (MAIT) cells are a unique T cell subset that contributes to protective immunity against microbial pathogens, but little is known about the role of chemokines in recruiting MAIT cells to the site of infection. Pulmonary infection with Francisella tularensis live vaccine strain (LVS) stimulates the accrual of large numbers of MAIT cells in the lungs of mice. Using this infection model, we find that MAIT cells are predominantly CXCR6+ but do not require CXCR6 for accumulation in the lungs. However, CXCR6 does contribute to long-term retention of MAIT cells in the airway lumen after clearance of the infection. We also find that MAIT cells are not recruited from secondary lymphoid organs and largely proliferate in situ in the lungs after infection. Nevertheless, the only known ligand for CXCR6, CXCL16, is sufficient to drive MAIT cell accumulation in the lungs in the absence of infection when administered in combination with the MAIT cell antigen 5-OP-RU. Overall, this new data advances the understanding of mechanisms that facilitate MAIT cell accumulation and retention in the lungs.

Highlights

Mucosa-associated invariant T (MAIT) cells are innate-like T cells that play important roles in protective immunity against microbial infections [1,2,3,4,5]
We further find that MAIT cell accumulation is not driven by recruitment from secondary lymphoid organs, and that the majority of MAIT cells proliferate in situ in the lungs after pulmonary F. tularensis live vaccine strain (LVS) infection
Fourteen days following primary sublethal F. tularensis LVS intranasal (IN) infection, Vα19iTg mice exhibited significant accumulation of MAIT cells as compared to their naïve counterparts in the lungs (24.1 ± 2.3% vs. 9.1 ± 0.7%, P < 0.01; 2.1 × 106 ± 7.2 × vs. 3.1 x ± 5.9 × 103 total MAIT cells/lung, P < 0.01), but no significant changes were observed in the spleen (4.8 ± 0.3% vs. 5.2 ± 0.3%), thymus (2.0 ± 0.5% vs. 3.0 ± 0.6%), and lamina propria (LP) (3.2 ± 0.4% vs. 1.9 ± 0.5%)

Summary

Introduction

Mucosa-associated invariant T (MAIT) cells are innate-like T cells that play important roles in protective immunity against microbial infections [1,2,3,4,5]. Riboflavin-related metabolites such as 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU) are present in many bacteria, yeast, and plants, but not in mammals and other animals [6,7,8]. Several pathogens such as Francisella tularensis live vaccine strain (LVS), Legionella longbeachae, and Salmonella typhimurium BRD509 have been reported to activate MAIT cells in vivo [9,10,11].

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Results

Conclusion