Functional and Phenotypic Changes of Natural Killer Cells in Whole Blood during Mycobacterium tuberculosis Infection and Disease.

Mathieu Garand,Simon Donkor,Beate Kampmann,Martin Goodier,Jayne S Sutherland,Olumuyiwa Owolabi

doi:10.3389/fimmu.2018.00257

Mathieu Garand, Simon Donkor + Show 4 more

Open Access

https://doi.org/10.3389/fimmu.2018.00257

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Abstract

Tuberculosis (TB) is still a global health concern, especially in resource-poor countries such as The Gambia. Defining protective immunity to TB is challenging: its pathogenesis is complex and involves several cellular components of the immune system. Recent works in vaccine development suggest important roles of the innate immunity in natural protection to TB, including natural killer (NK) cells. NK cells mediate cellular cytotoxicity and cytokine signaling in response to Mycobacterium tuberculosis (Mtb). NK cells can display specific memory-type markers to previous antigen exposure; thus, bridging innate and adaptive immunity. However, major knowledge gaps exist on the contribution of NK cells in protection against Mtb infection or TB. We performed a cross-sectional assessment of NK cells phenotype and function in four distinct groups of individuals: TB cases pre-treatment (n = 20) and post-treatment (n = 19), and household contacts with positive (n = 9) or negative (n = 18) tuberculin skin test (TST). While NK cells frequencies were similar between all groups, significant decreases in interferon-γ expression and degranulation were observed in NK cells from TB cases pre-treatment compared to post-treatment. Conversely, CD57 expression, a marker of advanced NK cells differentiation, was significantly lower in cases post-treatment compared to pre-treatment. Finally, NKG2C, an activation and imprinted-NK memory marker, was significantly increased in TST+ (latently infected) compared to TB cases pre-treatment and TST− (uninfected) individuals. The results of this study provide valuable insights into the role of NK cells in Mtb infection and TB disease, demonstrating potential markers for distinguishing between infection states and monitoring of TB treatment response.

Highlights

With an estimated 10.4 million new tuberculosis (TB) cases and 1.8 million deaths reported in 2015, TB is the leading cause of death from an infectious disease worldwide [1]
Evidence have recently emerged in regard to the importance of Frequency of major cell subsets analyzed by flow cytometry. (A) Dot plots showing the expression of CD57 and NKG2C on CD56dim CD16+ natural killer (NK) cells
We found that NK cells of active TB patients produced significantly reduced IFNγ and degranulation in response to Mycobacterium tuberculosis (Mtb)-specific antigens

Summary

Introduction

With an estimated 10.4 million new tuberculosis (TB) cases and 1.8 million deaths reported in 2015, TB is the leading cause of death from an infectious disease worldwide [1]. NK Cells and Mtb Infection no vaccines against any forms of adult TB [2] and no reliable biomarkers to distinguish latent from active TB status and, importantly, to determine the risk of developing the disease [3, 4]. Several immune mechanisms, involving CD4+, CD8+, and γδ T cells, have been shown to contribute to the control of Mtb after an infection has been established [5,6,7,8]. The most important feature of the adaptive immune response to TB is associated with CD4+ T cells production of interferon gamma (IFNγ), a critical factor for protection against the disease [9], and have been the subject of substantial research [reviewed in Ref [10]]. The overall T cell adaptive responses during TB are reviewed elsewhere [3, 11]

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