Cytotoxic cells kill intracellular bacteria through granulysin-mediated delivery of granzymes. (Cell, 2014, 157(6):1309-1323)

報告日期: 2014/10/28
報告時間: 3:10/4:00
報告學生: 謝承陸(以英文報告)
講評老師: 蔡佩珍
附件下載: 下載[1432-1412237628-1.pdf] 

Cytotoxic cells kill intracellular bacteria through granulysin-mediated delivery of granzymes

Walch, M., Dotiwala, F., Mulik, S., Thiery, J., Kirchhausen, T., Clayberger, C., Krensky, A.M., Martinvalet, D. and Lieberman, J.

Cell. (2014). 157, 1309-1323.

 

Speaker: Cheng-Lu Hsieh                              Date: 28 October 2014   15:10-16:00

Commentator: Dr. Pei-Jane Tsai                    Place: Room 602

 

 

Abstract

The natural killer cells (NK cells) are a kind of cytotoxic lymphocyte critical to the innate immune system. When host cells were infected with intracellular pathogens, NK cells recognized infected-cell and secreted perforin (PFN) and cytotoxic granzymes (Gzms) to trigger infected-cell apoptosis. It is known that NK cells participate the nonspecific antivirus activity. However, how NK cells kill intracellular bacteria is still unknown. Cytotoxic granules of humans contain a saposin-like pore-forming protein, granulysin (GNLY), which effectively disrupts cholesterol-pool bacterial cell membrane. Moreover, GNLY and Gzms were up-regulated when T cells were co-culture with intracellular bacteria. These cytotoxic effectors are suggested that these cytotoxic effectors might regulate intracellular bacteria survival.In this study, the authors co-cultured bacteria with these cytotoxic effectors and found that GNLY disrupts the bacterial memebrane to facilitate the entry of Gzms into bacterial to trigger bacterial death through the cleavage of electron transport chain complex I, generating superoxide anion. Treated Listeria monocytogenes infected HeLa cells with these cytotoxic effectors, they demonstrated that PFN generates pores allowing the delivery of GNLY and Gzms into the infected-cell. Using transgenic mice (Tg) with a GNLY gene specifically expressed in NK cells, they found Tg mice are more resistance to L. monocytogenes infection than WT mice. In this report, the authors demonstrated that NK cells kill intracellular bacteria through the secretion of PFN and then via GNLY-mediated delivery of Gzms to eliminate intracellular bacteria.

 

 

Reference

Walch, M., Rampini, S.K., Stoeckli, I., Latinovic-Golic, S., Dumrese, C., Sundstrom, H., Vogetseder, A., Marino, J., Glauser, D.L., van den Broek, M., et al. (2009). Involvement of CD252 (CD134L) and IL-2 in the expression of cytotoxic proteins in bacterial- or viral-activated human T cells. J. Immunol. 182, 7569-7579.