Streptococcus pyogenes SpyCEP Influences Host-Pathogen Interactions during Infection in a Murine Air Pouch Model

被引:22
作者
Chiappini, Nico [1 ]
Seubert, Anja [1 ]
Telford, John L. [1 ]
Grandi, Guido [1 ]
Serruto, Davide [1 ]
Margarit, Immaculada [1 ]
Janulczyk, Robert [1 ]
机构
[1] Novartis Vaccines & Diagnost, Res Ctr, Siena, Italy
关键词
GROUP-A STREPTOCOCCUS; CHEMOKINE DEGRADATION; BACTERIAL CLEARANCE; REGULATORY SYSTEM; INVASIVE DISEASE; PROTEASE SPYCEP; EXPRESSION; SURFACE; SEPSIS; GENE;
D O I
10.1371/journal.pone.0040411
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Streptococcus pyogenes is a major human pathogen worldwide, responsible for both local and systemic infections. These bacteria express the subtilisin-like protease SpyCEP which cleaves human IL-8 and related chemokines. We show that localization of SpyCEP is growth-phase and strain dependent. Significant shedding was observed only in a strain naturally overexpressing SpyCEP, and shedding was not dependent on SpyCEP autoproteolytic activity. Surface-bound SpyCEP in two different strains was capable of cleaving IL-8. To investigate SpyCEP action in vivo, we adapted the mouse air pouch model of infection for parallel quantification of bacterial growth, host immune cell recruitment and chemokine levels in situ. In response to infection, the predominant cells recruited were neutrophils, monocytes and eosinophils. Concomitantly, the chemokines KC, LIX, and MIP-2 in situ were drastically increased in mice infected with the SpyCEP knockout strain, and growth of this mutant strain was reduced compared to the wild type. SpyCEP has been described as a potential vaccine candidate against S. pyogenes, and we showed that surface-associated SpyCEP was recognized by specific antibodies. In vitro, such antibodies also counteracted the inhibitory effects of SpyCEP on chemokine mediated PMN recruitment. Thus, alpha-SpyCEP antibodies may benefit the host both directly by enabling opsonophagocytosis, and indirectly, by neutralizing an important virulence factor. The animal model we employed shows promise for broad application in the study of bacterial pathogenesis.
引用
收藏
页数:9
相关论文
共 37 条
[1]   Multi High-Throughput Approach for Highly Selective Identification of Vaccine Candidates: the Group A Streptococcus Case [J].
Bensi, Giuliano ;
Mora, Marirosa ;
Tuscano, Giovanna ;
Biagini, Massimiliano ;
Chiarot, Emiliano ;
Bombaci, Mauro ;
Capo, Sabrina ;
Falugi, Fabiana ;
Manetti, Andrea G. O. ;
Donato, Paolo ;
Swennen, Erwin ;
Gallotta, Marilena ;
Garibaldi, Manuela ;
Pinto, Vittoria ;
Chiappini, Nico ;
Musser, James M. ;
Janulczyk, Robert ;
Mariani, Massimo ;
Scarselli, Maria ;
Telford, John L. ;
Grifantini, Renata ;
Norais, Nathalie ;
Margarit, Immaculada ;
Grandi, Guido .
MOLECULAR & CELLULAR PROTEOMICS, 2012, 11 (06)
[2]   The global burden of group A streptococcal diseases [J].
Carapetis, JR ;
Steer, AC ;
Mulholland, EK ;
Weber, M .
LANCET INFECTIOUS DISEASES, 2005, 5 (11) :685-694
[3]  
CHEN CC, 1990, J BIOL CHEM, V265, P3161
[4]   Early Enhanced Local Neutrophil Recruitment in Peritonitis-Induced Sepsis Improves Bacterial Clearance and Survival [J].
Craciun, Florin L. ;
Schuller, Elizabeth R. ;
Remick, Daniel G. .
JOURNAL OF IMMUNOLOGY, 2010, 185 (11) :6930-6938
[5]   Macrophage-specific metalloelastase (MMP-12) truncates and inactivates ELR+CXC chemokines and generates CCL2,-7,-8, and-13 antagonists:: potential role of the macrophage in terminating polymorphonuclear leukocyte influx [J].
Dean, Richard A. ;
Cox, Jennifer H. ;
Bellac, Caroline L. ;
Doucet, Alain ;
Starr, Amanda E. ;
Overall, Christopher M. .
BLOOD, 2008, 112 (08) :3455-3464
[6]   An interaction between genetic factors and gender determines the magnitude of the inflammatory response in the mouse air pouch model of acute inflammation [J].
Delano, DL ;
Montesinos, MC ;
D'Eustachio, P ;
Wiltshire, T ;
Cronstein, BN .
INFLAMMATION, 2005, 29 (01) :1-7
[7]   TLR2-dependent eosinophil interactions with mycobacteria: role of α-defensins [J].
Driss, Virginie ;
Legrand, Fanny ;
Hermann, Emmanuel ;
Loiseau, Sylvie ;
Guerardel, Yann ;
Kremer, Laurent ;
Adam, Estelle ;
Woerly, Gaetane ;
Dombrowicz, David ;
Capron, Monique .
BLOOD, 2009, 113 (14) :3235-3244
[8]  
EDWARDS JCW, 1981, J PATHOL, V134, P147, DOI 10.1002/path.1711340205
[9]   Specific C-terminal cleavage and inactivation of interleukin-8 by invasive disease isolates of Streptococcus pyogenes [J].
Edwards, RJ ;
Taylor, GW ;
Ferguson, M ;
Murray, S ;
Rendell, N ;
Wrigley, A ;
Bai, ZH ;
Boyle, J ;
Finney, SJ ;
Jones, A ;
Russell, HH ;
Turner, C ;
Cohen, J ;
Faulkner, L ;
Sriskandan, S .
JOURNAL OF INFECTIOUS DISEASES, 2005, 192 (05) :783-790
[10]   Complete genome sequence of an M1 strain of Streptococcus pyogenes [J].
Ferretti, JJ ;
McShan, WM ;
Ajdic, D ;
Savic, DJ ;
Savic, G ;
Lyon, K ;
Primeaux, C ;
Sezate, S ;
Suvorov, AN ;
Kenton, S ;
Lai, HS ;
Lin, SP ;
Qian, YD ;
Jia, HG ;
Najar, FZ ;
Ren, Q ;
Zhu, H ;
Song, L ;
White, J ;
Yuan, XL ;
Clifton, SW ;
Roe, BA ;
McLaughlin, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (08) :4658-4663