Systemic immunization with rPotD reduces Streptococcus pneumoniae nasopharyngeal colonization in mice

被引:25
作者
Converso, T. R. [1 ,2 ]
Goulart, C. [1 ]
Rodriguez, D. [1 ]
Darrieux, M. [3 ]
Leite, L. C. C. [1 ]
机构
[1] Inst Butantan, Ctr Biotechnol, Sao Paulo, Brazil
[2] Programa Pos Grad Interunidades Biotecnol USP IPT, Sao Paulo, Brazil
[3] Univ Sao Francisco, Lab Biol Celular & Mol, Braganca Paulista, SP, Brazil
基金
巴西圣保罗研究基金会;
关键词
Streptococcus pneumoniae; PotD; Protein; Vaccine; Colonization; SURFACE PROTEIN-A; PNEUMOCOCCAL CONJUGATE VACCINE; POLYAMINE TRANSPORT; NITRIC-OXIDE; NASAL COLONIZATION; ESCHERICHIA-COLI; CHILDREN YOUNGER; POTD; INFECTION; PATHOGENESIS;
D O I
10.1016/j.vaccine.2016.11.027
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Streptococcus pneumoniae (pneumococcus) is a human pathogen that can cause otitis media, pneumonia and, in severe cases, meningitis and bacteremia. The pneumococcus expresses PotD, a protein belonging to the polyamines transporter complex called PotABCD. PotD is a membrane-associated protein that binds polyamines and has been shown to be important for virulence. In this work we demonstrate that subcutaneous immunization with rPotD reduces the bacterial load in the nasal tissue of mice, following intranasal challenge with a type 6B pneumococcus. The protective effect correlated with the induction of high levels of antibodies in the immunized group; the antibodies were able to increase bacterial phagocytosis by mouse peritoneal cells. The cellular immune response was characterized by the production of gamma-interferon, IL-2 and IL-17 by splenocytes and nitric oxide by peritoneal cells of immunized mice, upon stimulation with rPotD. Taken together our results suggest that PotD is a promising candidate to be included in a protein based pneumococcal vaccine, able to induce phagocytic antibodies, a Th1 cellular immune response and production of IL-17, reducing nasopharyngeal colonization, the main event responsible for transmission of pneumococci in humans. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码:149 / 155
页数:7
相关论文
共 40 条
[1]   Phenotypic characterization of Streptococcus pneumoniae biofilm development [J].
Allegrucci, M ;
Hu, FZ ;
Shen, K ;
Hayes, J ;
Ehrlich, GD ;
Post, JC ;
Sauer, K .
JOURNAL OF BACTERIOLOGY, 2006, 188 (07) :2325-2335
[2]  
[Anonymous], 2007, WKLY EPIDEMIOL REC
[3]   SOME ASPECTS OF THE PNEUMOCOCCAL CARRIER STATE [J].
AUSTRIAN, R .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1986, 18 :35-45
[4]   Nitric oxide and the immune response [J].
Bogdan, C .
NATURE IMMUNOLOGY, 2001, 2 (10) :907-916
[5]   The role of nitric oxide in innate immunity [J].
Bogdan, CT ;
Röllinghoff, M ;
Diefenbach, A .
IMMUNOLOGICAL REVIEWS, 2000, 173 :17-26
[6]   Polysaccharide Conjugate Vaccine against Pneumococcal Pneumonia in Adults [J].
Bonten, M. J. M. ;
Huijts, S. M. ;
Bolkenbaas, M. ;
Webber, C. ;
Patterson, S. ;
Gault, S. ;
van Werkhoven, C. H. ;
van Deursen, A. M. M. ;
Sanders, E. A. M. ;
Verheij, T. J. M. ;
Patton, M. ;
McDonough, A. ;
Moradoghli-Haftvani, A. ;
Smith, H. ;
Mellelieu, T. ;
Pride, M. W. ;
Crowther, G. ;
Schmoele-Thoma, B. ;
Scott, D. A. ;
Jansen, K. U. ;
Lobatto, R. ;
Oosterman, B. ;
Visser, N. ;
Caspers, E. ;
Smorenburg, A. ;
Emini, E. A. ;
Gruber, W. C. ;
Grobbee, D. E. .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (12) :1114-1125
[7]   Nasal colonization with Streptococcus pneumoniae includes subpopulations of surface and invasive pneumococci [J].
Briles, DE ;
Novak, L ;
Hotomi, M ;
van Ginkel, FW ;
King, J .
INFECTION AND IMMUNITY, 2005, 73 (10) :6945-6951
[8]   Immunizations with pneumococcal surface protein A and pneumolysin are protective against pneumonia in a murine model of pulmonary infection with Streptococcus pneumoniae [J].
Briles, DE ;
Hollingshead, SK ;
Paton, JC ;
Ades, EW ;
Novak, L ;
van Ginkel, FW ;
Benjamin, WH .
JOURNAL OF INFECTIOUS DISEASES, 2003, 188 (03) :339-348
[9]   Streptococcus pneumoniae biofilm formation and dispersion during colonization and disease [J].
Chao, Yashuan ;
Marks, Laura R. ;
Pettigrew, Melinda M. ;
Hakansson, Anders P. .
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 2015, 4
[10]   Current status and perspectives on protein-based pneumococcal vaccines [J].
Darrieux, Michelle ;
Goulart, Cibelly ;
Briles, David ;
de Cerqueira Leite, Luciana Cezar .
CRITICAL REVIEWS IN MICROBIOLOGY, 2015, 41 (02) :190-200