Part of the function of NK cells is to destroy cells that are unable to bind their KIR receptors. Or in other words, cells that don't express MHC class I. This is why they can kill MHC supressed infected- or tumor cells, which other immune cells can't.

However bacteria also don't express MHC-I. Yet NK cells are said to have very limited influence one microbial infections. I do not understand why NK cells do not degranulate (kill) bacteria upon finding that they do not have the MHC-I receptor complex.

Could someone elaborate this?

  • $\begingroup$ Human cells and bacteria are VERY different. Maybe an analogy would by be a police unit instructed to check in on all houses that don't have letter boxes. If they come across an area with tents, shacks or similar (which obviously don't have letter boxes) they'll still ignore it, just because those aren't houses in the first place. $\endgroup$
    – Nicolai
    May 23, 2019 at 16:55

1 Answer 1


While you’re correct that NK cells are often activated (in part) by the absence of MHC-I, they require other signaling events to become fully activated:

The Molecular Mechanism of Natural Killer Cells Function and Its Importance in Cancer Immunotherapy. Paul & Lal. Frontiers in Immunology. 2017.

Activating Receptors on NK Cells

Lack of MHC class I on the target cell is not sufficient to trigger NK cell activation. Full NK cell activation also requires recognition of stress-induced molecules by NK cell activating receptors.

Natural cytotoxicity receptors (NCRs) are another immunoglobulin superfamily of activating receptors that utilize extracellular immunoglobulin-like domain for ligand binding. Human NK cells express three distinct types of NCRs... NCRs recognize a wide variety of ligands on target cells ranging from viral, bacterial and parasite proteins to molecules from tumor cells and other host cells.

Role of natural killer cells in antibacterial immunity. Schmidt et al. Expert Review of Hematology. 2016.

6 Bacteria fight back and inhibit NK cell activities

During evolution, many bacteria have developed survival strategies which counteract NK cell activity.

Both Gram-positive bacteria such as Streptococcus pneumoniae and Gram-negative bacteria such as Salmonella spp and Escherichia coli are able to induce prostaglandin E2 (PGE2), which negatively affects NK cell functions at different levels. PGE2 inhibits the cytolytic activities of NK cells by suppressing their responsiveness to cytokines such as IL-12 and IL-15, and suppresses NK cell mediated activation of macrophages by inhibiting the production of IFN-γ. Similarly, PGE2 has a deleterious effect on homing, migration, and survival of NK cells, as it has been shown in Human Herpes Virus 8 (HHV8) infection. Thus, bacteria are able to inhibit both cytotoxic and immunoregulatory effects of NK cells in various ways.

8 Conclusions

In conclusion, there is a growing body of evidence that NK cells play an important role in the antibacterial host response. NK cells are able to kill bacteria directly, or to modulate the immune system via cytokines and interferons. Further studies are needed to characterize how NK cells are activated by different bacteria. In addition, the role of NK cells among the other arms of the immune system in the defense against bacteria is poorly understood. Last, bacteria are able to inhibit NK cell activities, and a better understanding of this impairment may be the basis to specifically strengthen the antibacterial host response. Therefore, additional in vitro and in vivo data may open new therapeutic strategies using NK cells to fight bacterial infections.

If you’d like a full-text copy of the Schmidt paper, I can share it with you.


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