Uncovering an Important Role for YopJ in the Inhibition of Caspase-1 in Activated Macrophages and Promoting Yersinia pseudotuberculosis Virulence

被引:15
作者
Schoberle, Taylor J. [1 ,2 ]
Chung, Lawton K. [1 ,2 ]
McPhee, Joseph B. [3 ]
Bogin, Ben [4 ]
Bliska, James B. [1 ,2 ]
机构
[1] SUNY Stony Brook, Ctr Infect Dis, Stony Brook, NY 11794 USA
[2] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA
[3] Ryerson Univ, Dept Biol & Chem, Toronto, ON, Canada
[4] Middlebury Coll, Middlebury, VT 05753 USA
关键词
III SECRETION SYSTEM; INNATE IMMUNE-RESPONSES; NF-KAPPA-B; CELL-DEATH; INFLAMMASOME ACTIVATION; GAMMA-INTERFERON; EPITHELIAL-CELLS; HOST DEFENSES; EFFECTOR YOPJ; BACTERIAL;
D O I
10.1128/IAI.00843-15
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Pathogenic Yersinia species utilize a type III secretion system to translocate Yop effectors into infected host cells. Yop effectors inhibit innate immune responses in infected macrophages to promote Yersinia pathogenesis. In turn, Yersinia-infected macrophages respond to translocation of Yops by activating caspase-1, but different mechanisms of caspase-1 activation occur, depending on the bacterial genotype and the state of phagocyte activation. In macrophages activated with lipopolysaccharide (LPS) prior to Yersinia pseudotuberculosis infection, caspase-1 is activated by a rapid inflammasome-dependent mechanism that is inhibited by translocated YopM. The possibility that other effectors cooperate with YopM to inhibit caspase-1 activation in LPS-activated macrophages has not been investigated. Toward this aim, epistasis analysis was carried out in which the phenotype of a Y. pseudotuberculosis yopM mutant was compared to that of a yopJ yopM, yopE yopM, yopH yopM, yopT yopM, or ypkA yopM mutant. Activation of caspase-1 was measured by cleavage of the enzyme, release of interleukin-1 beta (IL-1 beta), and pyroptosis in LPS-activated macrophages infected with wild-type or mutant Y. pseudotuberculosis strains. Results show enhanced activation of caspase-1 after infection with the yopJ yopM mutant relative to infection by any other single or double mutant. Similar results were obtained with the yopJ, yopM, and yopJ yopM mutants of Yersinia pestis. Following intravenous infection of mice, the Y. pseudotuberculosis yopJ mutant was as virulent as the wild type, while the yopJ yopM mutant was significantly more attenuated than the yopM mutant. In summary, through epistasis analysis this work uncovered an important role for YopJ in inhibiting caspase-1 in activated macrophages and in promoting Yersinia virulence.
引用
收藏
页码:1062 / 1072
页数:11
相关论文
共 64 条
[31]   Yersinia pseudotuberculosis Effector YopJ Subverts the Nod2/RICK/TAK1 Pathway and Activates Caspase-1 to Induce Intestinal Barrier Dysfunction [J].
Meinzer, Ulrich ;
Barreau, Frederick ;
Esmiol-Welterlin, Sophie ;
Jung, Camille ;
Villard, Claude ;
Leger, Thibaut ;
Ben-Mkaddem, Sanah ;
Berrebi, Dominique ;
Dussaillant, Monique ;
Alnabhani, Ziad ;
Roy, Maryline ;
Bonacorsi, Stephane ;
Wolf-Watz, Hans ;
Perroy, Julie ;
Ollendorff, Vincent ;
Hugot, Jean-Pierre .
CELL HOST & MICROBE, 2012, 11 (04) :337-351
[32]   Acetylation of MEK2 and IκB kinase (IKK) activation loop residues by YopJ inhibits signaling [J].
Mittal, Rohit ;
Peak-Chew, Sew-Yeu ;
McMahon, Harvey T. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (49) :18574-18579
[33]   The Acetyltransferase Activity of the Bacterial Toxin YopJ of Yersinia Is Activated by Eukaryotic Host Cell Inositol Hexakisphosphate [J].
Mittal, Rohit ;
Peak-Chew, Sew Yeu ;
Sade, Robert S. ;
Vallis, Yvonne ;
McMahon, Harvey T. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (26) :19927-19934
[34]   NOD-LIKE RECEPTORS: VERSATILE CYTOSOLIC SENTINELS [J].
Motta, Vinicius ;
Soares, Fraser ;
Sun, Tian ;
Philpott, Dana J. .
PHYSIOLOGICAL REVIEWS, 2015, 95 (01) :149-178
[35]   Yersinia YopJ acetylates and inhibits kinase activation by blocking phosphorylation [J].
Mukherjee, Sohini ;
Keitany, Gladys ;
Li, Yan ;
Wang, Yong ;
Ball, Haydn L. ;
Goldsmith, Elizabeth J. ;
Orth, Kim .
SCIENCE, 2006, 312 (5777) :1211-1214
[36]   Functions of the Yersinia effector proteins in inhibiting host immune responses [J].
Navarro, L ;
Alto, NM ;
Dixon, JE .
CURRENT OPINION IN MICROBIOLOGY, 2005, 8 (01) :21-27
[37]   Serine/threonine acetylation of TGFβ-activated kinase (TAK1) by Yersinia pestis YopJ inhibits innate immune signaling [J].
Paquette, Nicholas ;
Conlon, Joseph ;
Sweet, Charles ;
Rus, Florentina ;
Wilson, Lindsay ;
Pereira, Andrea ;
Rosadini, Charles V. ;
Goutagny, Nadege ;
Weber, Alexander N. R. ;
Lane, William S. ;
Shaffer, Scott A. ;
Maniatis, Stephanie ;
Fitzgerald, Katherine A. ;
Stuart, Lynda ;
Silverman, Neal .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (31) :12710-12715
[38]   Caspase-8 mediates caspase-1 processing and innate immune defense in response to bacterial blockade of NF-κB and MAPK signaling [J].
Philip, Naomi H. ;
Dillon, Christopher P. ;
Snyder, Annelise G. ;
Fitzgerald, Patrick ;
Wynosky-Dolfi, Meghan A. ;
Zwack, Erin E. ;
Hu, Baofeng ;
Fitzgerald, Louise ;
Mauldin, Elizabeth A. ;
Copenhaver, Alan M. ;
Shin, Sunny ;
Wei, Lei ;
Parker, Matthew ;
Zhang, Jinghui ;
Oberst, Andrew ;
Green, Douglas R. ;
Brodsky, Igor E. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (20) :7385-7390
[39]   Cell death programs in Yersinia immunity and pathogenesis [J].
Philip, Naomi H. ;
Brodsky, Igore E. .
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 2012, 2 :149
[40]   The Yersinia pestis type III secretion system: expression, assembly and role in the evasion of host defenses [J].
Plano, Gregory V. ;
Schesser, Kurt .
IMMUNOLOGIC RESEARCH, 2013, 57 (1-3) :237-245