Salmonella enterica Serovar Typhimurium Invades Fibroblasts by Multiple Routes Differing from the Entry into Epithelial Cells

被引:53
作者
Aiastui, Ana [1 ]
Graciela Pucciarelli, M. [1 ,2 ]
Garcia-del Portillo, Francisco [1 ]
机构
[1] CSIC, Ctr Nacl Biotecnol, Dept Biotecnol Microbiana, Madrid 28049, Spain
[2] Univ Autonoma Madrid, Dept Biol Mol, E-28049 Madrid, Spain
关键词
HOST-CELL; ACTIN CYTOSKELETON; RHO GTPASES; COORDINATE REGULATION; SECRETION SYSTEM; LIFE-SPAN; INVASION; MEMBRANE; EXPRESSION; REQUIRES;
D O I
10.1128/IAI.01389-09
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Fibroblasts are ubiquitous cells essential to tissue homeostasis. Despite their nonphagocytic nature, fibroblasts restrain replication of intracellular bacterial pathogens such as Salmonella enterica serovar Typhimurium. The extent to which the entry route of the pathogen determines this intracellular response is unknown. Here, we analyzed S. Typhimurium invasion in fibroblasts obtained from diverse origins, including primary cultures and stable nontransformed cell lines derived from normal tissues. Features distinct to the invasion of epithelial cells were found in all fibroblasts tested. In some fibroblasts, bacteria lacking the type III secretion system encoded in the Salmonella pathogenicity island 1 displayed significant invasion rates and induced the formation of lamellipodia and filopodia at the fibroblast-bacteria contact site. Other bacterial invasion traits observed in fibroblasts were the requirement of phosphatidylinositol 3-kinase, mitogen-activated protein kinase MEK1, and both actin filaments and microtubules. RNA interference studies showed that different Rho family GTPases are targeted by S. Typhimurium to enter into distinct fibroblasts. Rac1 and Cdc42 knockdown affected invasion of normal rat kidney fibroblasts, whereas none of the GTPases tested (Rac1, Cdc42, RhoA, or RhoG) was essential for invasion of immortalized human foreskin fibroblasts. Collectively, these data reveal a marked diversity in the modes used by S. Typhimurium to enter into fibroblasts.
引用
收藏
页码:2700 / 2713
页数:14
相关论文
共 86 条
[1]   Rho GTPases have diverse effects on the organization of the actin filament system [J].
Aspenström, P ;
Fransson, Å ;
Saras, J .
BIOCHEMICAL JOURNAL, 2004, 377 :327-337
[2]   Salmonella-Containing Vacuoles: Directing Traffic and Nesting to Grow [J].
Bakowski, Malina A. ;
Braun, Virginie ;
Brumell, John H. .
TRAFFIC, 2008, 9 (12) :2022-2031
[3]  
Baumler AJ, 1996, INFECT IMMUN, V64, P1862
[4]   Three-dimensional organotypic models of human colonic epithelium to study the early stages of enteric salmonellosis [J].
Bentrup, Kerstin Honer zu ;
Ramamurthy, Rajee ;
Ott, C. Mark ;
Emami, Kamal ;
Nelman-Gonzalez, Mayra. ;
Wilson, James W. ;
Richter, Emily G. ;
Goodwin, Thomas J. ;
Alexander, J. Stephen ;
Pierson, Duane L. ;
Pellis, Neal ;
Buchanan, Kent L. ;
Nickerson, Cheryl A. .
MICROBES AND INFECTION, 2006, 8 (07) :1813-1825
[5]   Interaction of Salmonella enterica serovar Typhi with cultured epithelial cells:: roles of surface structures in adhesion and invasion [J].
Bishop, Anne ;
House, Deborah ;
Perkins, Timothy ;
Baker, Stephen ;
Kingsley, Robert A. ;
Dougan, Gordon .
MICROBIOLOGY-SGM, 2008, 154 :1914-1926
[6]   Role of microfilaments and microtubules in the invasion of INT-407 cells by Campylobacter jejuni [J].
Biswas, D ;
Itoh, K ;
Sasakawa, C .
MICROBIOLOGY AND IMMUNOLOGY, 2003, 47 (06) :469-473
[7]   Extension of life-span by introduction of telomerase into normal human cells [J].
Bodnar, AG ;
Ouellette, M ;
Frolkis, M ;
Holt, SE ;
Chiu, CP ;
Morin, GB ;
Harley, CB ;
Shay, JW ;
Lichtsteiner, S ;
Wright, WE .
SCIENCE, 1998, 279 (5349) :349-352
[8]   Fibroblasts as host cells in latent leishmaniosis [J].
Bogdan, C ;
Donhauser, N ;
Döring, R ;
Röllinghoff, M ;
Diefenbach, A ;
Rittig, MG .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 191 (12) :2121-2129
[9]   IQGAP1 regulates Salmonella invasion through interactions with actin, Rac1, and Cdc42 [J].
Brown, Matthew D. ;
Bry, Lynn ;
Li, Zhigang ;
Sacks, David B. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (41) :30265-30272
[10]   Invasion of HeLa cells by group B streptococcus requires the phosphoinositide-3-kinase signalling pathway and modulates phosphorylation of hostcell Akt and glycogen synthase kinase-3 [J].
Burnham, Carey-Ann D. ;
Shokoples, Sandra E. ;
Tyrrell, Gregory J. .
MICROBIOLOGY-SGM, 2007, 153 :4240-4252