Title

NK cells kill mycobacteria directly by releasing perforin and granulysin

ORCiD

David M. Ojcius: 0000-0003-1461-4495

Document Type

Article

Publication Title

Journal of Leukocyte Biology

ISSN

0741-5400

Volume

96

Issue

6

DOI

10.1189/jlb.4A0713-363RR

First Page

1119

Last Page

1129

Publication Date

12-1-2014

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.