Related Experiment Video
Updated: Apr 25, 2026

A Flow Cytometry-Based Cytotoxicity Assay for the Assessment of Human NK Cell Activity
Published on: August 9, 2017
NK cells kill mycobacteria directly by releasing perforin and granulysin
Chia-Chen Lu1, Ting-Shu Wu2, Ya-Jing Hsu3
1Department of Respiratory Therapy, College of Medicine, Fu Jen Catholic University, Taipei, Taiwan;
Abstract:
Although the mechanisms underlying the cytotoxic effect of NK cells on tumor cells and intracellular bacteria have been studied extensively, it remains unclear how these cells kill extracellular bacterial pathogens. In this study, we examine how human NK cells kill Mycobacterium kansasii and M.tb. The underlying mechanism is contact dependent and requires two cytolytic proteins: perforin and granulysin. Mycobacteria induce enhanced expression of the cytolytic proteins via activation of the NKG2D/NCR cell-surface receptors and intracellular signaling pathways involving ERK, JNK, and p38 MAPKs. These results suggest that NK cells use similar cellular mechanisms to kill both bacterial pathogens and target host cells. This report reveals a novel role for NK cells, perforin, and granulysin in killing mycobacteria and highlights a potential alternative defense mechanism that the immune system can use against mycobacterial infection.
Insights
Natural killer (NK) cells kill extracellular bacteria like Mycobacterium using perforin and granulysin. This mechanism, activated by specific receptors, offers a new defense against mycobacterial infections.
Area of Science:
- Immunology
- Microbiology
- Cellular Biology
Background:
- Natural killer (NK) cells are crucial for immunity against tumors and intracellular pathogens.
- Mechanisms of NK cell cytotoxicity against extracellular bacteria, particularly mycobacteria, are not well understood.
Purpose of the Study:
- To investigate how human NK cells kill extracellular bacterial pathogens, specifically Mycobacterium kansasii and Mycobacterium tuberculosis (M.tb).
- To elucidate the molecular mechanisms and cellular pathways involved in NK cell-mediated killing of mycobacteria.
Main Methods:
- Co-culture of human NK cells with Mycobacterium species.
- Analysis of cytolytic protein expression (perforin, granulysin).
- Assessment of cell-surface receptor activation (NKG2D/NCR) and intracellular signaling pathways (ERK, JNK, p38 MAPKs).
Main Results:
- NK cell-mediated killing of mycobacteria is contact-dependent.
- Perforin and granulysin are essential cytolytic proteins for this process.
- Mycobacteria activate NKG2D/NCR receptors, leading to enhanced perforin and granulysin expression via ERK, JNK, and p38 MAPK signaling.
Conclusions:
- NK cells employ similar cytotoxic mechanisms against mycobacteria as they do against tumor cells and intracellular pathogens.
- This study reveals a novel role for NK cells, perforin, and granulysin in combating mycobacterial infections.
- Identifies a potential alternative immune defense strategy against mycobacterial diseases.
Related Concept Videos
Cells of the Innate Immune Response
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immune Surveillance by NK Cells and Phagocytes
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
Immune Response Against Viral Pathogens
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
Phagocytosis of Apoptotic Cells
Normal cells contain receptors that prevent them from being recognized...
The Extrinsic Apoptotic Pathway

