Memory of Natural Killer Cells: A New Chance against Mycobacterium tuberculosis?

Abstract

Natural killer (NK) cells are lymphocytes of the innate immune system, which play an important role in the initial defense against a wide variety of pathogens, including viruses and intracellular bacteria. NK cells produce cytokines that enhance immune responses directed toward pathogens and also exert cytotoxic activity against infected cells, thereby eliminating the reservoir of infection. Their role in defense against Mycobacterium tuberculosis (Mtb) has been recently studied, and there is increasing evidence that highlight the importance of NK cell function during pulmonary tuberculosis (PTB), especially in the absence of optimal T-cell responses. Additionally, in the last years, it has been observed that NK cells mediate secondary responses against antigens to which they were previously exposed, an ability classically attributed to lymphocytes of the adaptive branch of immunity. This phenomenon, called “innate memory,” could have important implications in the efforts to develop therapies and vaccines to improve the initial phases of immune reactions against different microorganisms, especially those to which there is not yet available vaccines to prevent infection, as is the case for tuberculosis. Therefore, the possibility of inducing memory-like NK cells ready to act prior to contact with Mtb or during the earliest stages of infection becomes quite interesting. However, our understanding of the mechanisms of innate memory remains incomplete. Here, we review recent literature about the mechanisms involved in the formation and maintenance of NK cell memory and the role of these cells in the immune response during tuberculosis. Finally, we discuss if the current evidence is sufficient to substantiate that NK cells exert more rapid and robust secondary responses after consecutive encounters with Mtb.

Strategies to Improve Vaccine Efficacy against Tuberculosis by Targeting Innate Immunity

“…However, upon infection, NK cells were found to display a memory-like phenotype providing so-called innate memory ( 121 – 123 ). This phenomenon has also been described upon M. tuberculosis infection ( 124 ). For instance, NK cells recovered from pleural fluid from tuberculosis patients were a major source of IFN-γ as well as IL-22 production when restimulated with M. tuberculosis ex vivo ( 125 , 126 ).…”

Meta-Analysis Identification of Highly Robust and Differential Immune-Metabolic Signatures of Systemic Host Response to Acute and Latent Tuberculosis in Children and Adults

“…This meta-analysis which combined studies from different locations further strengthens evidence for the important contribution of neutrophils in TB. Proportions of monocytes and activated NK cells were also higher in active TB compared to controls, and NK cells have been shown to play an important role in combating mycobacterial infections ( Allen et al, 2015 ; Choreño Parra et al, 2017 ). However, proportions of resting NK cells were lower in active TB compared to LTBI individuals and uninfected controls which agrees with previous studies ( Kee et al, 2012 ).…”

Host-Directed Therapy as a Novel Treatment Strategy to Overcome Tuberculosis: Targeting Immune Modulation

“…Moreover, NK cells also have the capacity to indirectly stimulate immune responses through the activation of macrophages with multiple signaling pathways, including generation of both reactive oxygen species (ROS) and reactive nitrogen species (RNS) [25]. Mtb-infected macrophages can be destroyed directly by NK cells, whereby the NK cells mount a pro-inflammatory response in an apoptosis-dependent manner [26].…”