Mucosal-Associated Invariant T Cell Levels Are Reduced in the Peripheral Blood and Lungs of Children With Active Pulmonary Tuberculosis.

Clara Malka-Ruimy,Sophie Caillat-Zucman,Liana Ghazarian,Albert Faye,Marie Tourret,Véronique Houdouin,Marion Lambert,Ghada Ben Youssef

doi:10.3389/fimmu.2019.00206

Abstract

Mucosal associated invariant T (MAIT) cells are unconventional, semi-invariant T lymphocytes that recognize microbial-derived vitamin B2 (riboflavin) biosynthesis precursor derivatives presented by the monomorphic MHC class 1-related (MR1) molecule. Upon microbial infection, MAIT cells rapidly produce cytokines and cytotoxic effectors, and are thus important players in anti-microbial defense. MAIT cells are protective in experimental models of infection and are decreased in the blood of adult patients with bacterial infections, including Mycobacterium tuberculosis (Mtb). In children, the risk of rapid progression to active tuberculosis (TB) following Mtb infection is higher than in adults. Whether MAIT cells influence the outcome of Mtb infection in children is therefore, an important issue. We analyzed MAIT cell numbers and phenotype in 115 children investigated for pulmonary TB and determined their potential correlation with disease progression. MAIT cells were reduced in numbers and activated in the peripheral blood of children with active TB as compared to those with latent TB infection (LTBI) and healthy children. Moreover, MAIT cells did not accumulate and did not proliferate in the lung of children with active TB. These results suggest that MAIT cells may be important in preventing progression of Mtb infection to active TB in children.

Highlights

Tuberculosis (TB) in children remains a major diagnosis challenge, due to the non-specific nature of most clinical symptoms and lack of accurate and rapid microbiological confirmation of active Mycobacterium tuberculosis (Mtb) infection [1]
We quantified peripheral blood Mucosal associated invariant T (MAIT) cells in 115 children investigated for pulmonary TB and further classified as acute TB, latent TB infection (LTBI), and exposed non-infected (NI) children, in comparison to 58 healthy children (HC)
Our results show that MAIT cells are numerically deficient in the peripheral blood of children with active TB as compared to LTBI and healthy children

Summary

INTRODUCTION

Tuberculosis (TB) in children remains a major diagnosis challenge, due to the non-specific nature of most clinical symptoms and lack of accurate and rapid microbiological confirmation of active Mycobacterium tuberculosis (Mtb) infection [1]. MAIT cells are abundant in the peripheral blood, liver and mucosal tissues (lung and gut) [7, 8, 13] Their frequencies are decreased in the blood of patients with various bacterial infections [14,15,16], suggesting that they are recruited from the peripheral blood to the infected tissues. MAIT cells are found in the lungs or pleural effusions of patients with active TB [7, 23], but whether their reduction in the periphery is related to their migration to Mtb-infected tissues remains unclear. We analyzed MAIT cells numbers and phenotype in a cohort of 115 children investigated for pulmonary TB, and determined their potential correlation with the outcome of Mtb infection.

RESULTS

DISCUSSION

ETHICS STATEMENT