Intimin-specific immune responses prevent bacterial colonization by the attaching-effacing pathogen Citrobacter rodentium

被引:75
作者
Ghaem-Maghami, M
Simmons, CP [1 ]
Daniell, S
Pizza, M
Lewis, D
Frankel, G
Dougan, G
机构
[1] Univ London Imperial Coll Sci Technol & Med, Dept Biochem, Ctr Mol Microbiol & Infect, London SW7 2AZ, England
[2] St George Hosp, Sch Med, Dept Infect Dis, London SW17 0RE, England
[3] Chiron Vaccines Immunol Res Inst, I-53100 Siena, Italy
关键词
D O I
10.1128/IAI.69.9.5597-5605.2001
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The formation of attaching and effacing (A/E) lesions on gut enterocytes is central to the pathogenesis of enterohemorrhagic (EHEC) Escherichia coli, enteropathogenic E. coli (EPEC), and the rodent pathogen Citrobacter rodentium. Genes encoding A/E lesion formation map to a chromosomal pathogenicity island termed the locus of enterocyte effacement (LEE). Here we show that the LEE-encoded proteins EspA, EspB, Tir, and intimin are the targets of long-lived humoral immune responses in C. rodentium-infected mice. Mice infected with C. rodentium developed robust acquired immunity and were resistant to reinfection with wild-type C. rodentium or a C. rodentium derivative, DBS255(pCVD438), which expressed intimin derived from EPEC strain E2348/69. The receptor-binding domain of intimin polypeptides is located within the carboxy-terminal 280 amino acids (Int280). Mucosal and systemic vaccination regimens using enterotoxin-based adjuvants were employed to elicit immune responses to recombinant Int280 alpha from EPEC strain E2348/69. Mice vaccinated subcutaneously with Int280 alpha, in the absence of adjuvant, were significantly more resistant to oral challenge with DBS255(pCVD438) but not with wild-type C. rodentium. This type-specific immunity could not be overcome by employing an exposed, highly conserved domain of intimin (Int(388-667)) as a vaccine. These results show that anti-intimin immune responses can modulate the outcome (of a C rodentium infection and support the use of intimin as a component of a type-specific EPEC or EHEC vaccine.
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页码:5597 / 5605
页数:9
相关论文
共 45 条
[1]   Detection of intimins α, β, γ, and δ, four intimin derivatives expressed by attaching and effacing microbial pathogens [J].
Adu-Bobie, J ;
Frankel, G ;
Bain, C ;
Goncalves, AG ;
Trabulsi, LR ;
Douce, G ;
Knutton, S ;
Dougan, G .
JOURNAL OF CLINICAL MICROBIOLOGY, 1998, 36 (03) :662-668
[2]   Presence of the LEE (locus of enterocyte effacement) in pig attaching and effacing Escherichia coli and characterization of eae, espA, espB and espD genes of PEPEC (pig EPEC) strain 1390 [J].
An, HY ;
Fairbrother, JM ;
Désautels, C ;
Mabrouk, T ;
Dugourd, D ;
Dezfulian, H ;
Harel, J .
MICROBIAL PATHOGENESIS, 2000, 28 (05) :291-300
[3]   TRANSMISSIBLE MURINE COLONIC HYPERPLASIA [J].
BARTHOLD, SW ;
COLEMAN, GL ;
JACOBY, RO ;
LIVSTONE, EM ;
JONAS, AM .
VETERINARY PATHOLOGY, 1978, 15 (02) :223-236
[4]  
BARTHOLD SW, 1980, LAB ANIM SCI, V30, P167
[5]   Development of a universal intimin antiserum and PCR primers [J].
Batchelor, M ;
Knutton, S ;
Caprioli, A ;
Huter, V ;
Zanial, M ;
Dougan, G ;
Frankel, G .
JOURNAL OF CLINICAL MICROBIOLOGY, 1999, 37 (12) :3822-3827
[6]  
Beutin L, 1999, VET RES, V30, P285
[7]   Diversity of antibody-mediated immunity at the mucosal barrier [J].
Bouvet, JP ;
Fischetti, VA .
INFECTION AND IMMUNITY, 1999, 67 (06) :2687-2691
[8]   Heterogeneity of the eae genes in attaching effacing Escherichia coli from cattle:: comparison with human strains [J].
China, B ;
Jacquemin, E ;
Devrin, AC ;
Pirson, V ;
Mainil, J .
RESEARCH IN MICROBIOLOGY, 1999, 150 (05) :323-332
[9]   Double-blind vaccine-controlled randomised efficacy trial of an investigational Shigella sonnei conjugate vaccine in young adults [J].
Cohen, D ;
Ashkenazi, S ;
Green, MS ;
Gdalevich, M ;
Robin, G ;
Slepon, R ;
Yavzori, M ;
Orr, N ;
Block, C ;
Ashkenazi, I ;
Shemer, J ;
Taylor, DN ;
Hale, TL ;
Sadoff, JC ;
Pavliakova, D ;
Schneerson, R ;
Robbins, JB .
LANCET, 1997, 349 (9046) :155-159
[10]   ROLE OF THE EAEA GENE IN EXPERIMENTAL ENTEROPATHOGENIC ESCHERICHIA-COLI INFECTION [J].
DONNENBERG, MS ;
TACKET, CO ;
JAMES, SP ;
LOSONSKY, G ;
NATARO, JP ;
WASSERMAN, SS ;
KAPER, JB ;
LEVINE, MM .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 92 (03) :1412-1417