This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bergeron, Y.
Right arrow Articles by Bergeron, M. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bergeron, Y.
Right arrow Articles by Bergeron, M. G.

 Previous Article  |  Next Article 

Infect Immun, March 1998, p. 912-922, Vol. 66, No. 3
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Cytokine Kinetics and Other Host Factors in Response to Pneumococcal Pulmonary Infection in Mice

Yves Bergeron, Nathalie Ouellet, Anne-Marie Deslauriers, Marie Simard, Martin Olivier, and Michel G. Bergeron*

Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval, and Département de Microbiologie, Faculté de Médecine, Université Laval, Québec, Canada G1V 4G2

Received 29 August 1997/Returned for modification 14 October 1997/Accepted 5 December 1997

There is a need for more insight into the pathogenesis of Streptococcus pneumoniae pneumonia, as the fatality rate associated with this disease remains high despite appropriate antibiotherapy. The host response to pneumococci was investigated after intranasal inoculation of CD1 mice with 107 log-phase CFU of bacteria. We identified five major pathogenesis steps from initial infection to death. In step 1 (0 to 4 h), there was ineffective phagocytosis by alveolar macrophages, with concurrent release of tumor necrosis factor alpha (TNF), interleukin-6 (IL-6), and nitric oxide (NO) in bronchoalveolar lavage (BAL) fluid, TNF, IL-6, and interleukin-1 alpha (IL-1) in lung tissues, and IL-6 in serum, which were associated with tachypnea and hemoconcentration. In step 2 (4 to 24 h), bacterial growth in alveoli and polymorphonuclear cell recruitment from bloodstream to lung tissue (high myeloperoxidase levels) to alveoli were associated with high release of all three cytokines and leukotriene B4 (LTB4) in tissue and BAL fluid, as well as transient spillover of IL-1 in serum. In step 3 (24 to 48 h), despite downregulation of TNF and IL-1 in BAL fluid and lungs, there was appearance of injury to alveolar ultrastructure, edema to interstitium, and increase in lung weight as well as regeneration of type II pneumocytes and increased secretion of surfactant; bacteria progressed from alveoli to tissue to blood, and body weight loss occurred. In step 4 (48 to 72 h), strong monocyte recruitment from blood to alveoli was associated with high NO release in tissue and BAL fluid, but there was also noticeable lymphocyte recruitment and leukopenia; bacteremia was associated with TNF and IL-6 release in blood and thrombocytopenia. In step 5 (72 to 96 h), severe airspace disorganization, lipid peroxidation (high malondialdehyde release in BAL fluid), and diffuse tissue damage coincided with high NO levels; there was further increase in lung weight and bacterial growth, loss in body weight, and high mortality rate. Delineation of the sequential steps that contribute to the pathogenesis of pneumococcal pneumonia may generate markers of evolution of disease and lead to better targeted intervention.

* Corresponding author. Mailing address: Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval, 2705 Boul. Laurier, Sainte-Foy, Québec, Canada G1V 4G2. Phone: (418) 654-2705. Fax: (418) 654-2715. E-mail: Michel.G.Bergeron{at}crchul.ulaval.ca.




This article has been cited by other articles:

  • Giebelen, I. A. J., Leendertse, M., Florquin, S., van der Poll, T. (2009). Stimulation of acetylcholine receptors impairs host defence during pneumococcal pneumonia. Eur Respir J 33: 375-381 [Abstract] [Full Text]  
  • Chiavolini, D., Pozzi, G., Ricci, S. (2008). Animal Models of Streptococcus pneumoniae Disease. Clin. Microbiol. Rev. 21: 666-685 [Abstract] [Full Text]  
  • Kafka, D., Ling, E., Feldman, G., Benharroch, D., Voronov, E., Givon-Lavi, N., Iwakura, Y., Dagan, R., Apte, R. N., Mizrachi-Nebenzahl, Y. (2008). Contribution of IL-1 to resistance to Streptococcus pneumoniae infection. Int Immunol 20: 1139-1146 [Abstract] [Full Text]  
  • Calbo, E., Alsina, M., Rodriguez-Carballeira, M., Lite, J., Garau, J. (2008). Systemic Expression of Cytokine Production in Patients with Severe Pneumococcal Pneumonia: Effects of Treatment with a {beta}-Lactam versus a Fluoroquinolone. Antimicrob. Agents Chemother. 52: 2395-2402 [Abstract] [Full Text]  
  • Raquil, M.-A., Anceriz, N., Rouleau, P., Tessier, P. A. (2008). Blockade of Antimicrobial Proteins S100A8 and S100A9 Inhibits Phagocyte Migration to the Alveoli in Streptococcal Pneumonia. J. Immunol. 180: 3366-3374 [Abstract] [Full Text]  
  • Nieminen, J., St-Pierre, C., Bhaumik, P., Poirier, F., Sato, S. (2008). Role of Galectin-3 in Leukocyte Recruitment in a Murine Model of Lung Infection by Streptococcus pneumoniae. J. Immunol. 180: 2466-2473 [Abstract] [Full Text]  
  • Mahdi, L. K., Ogunniyi, A. D., LeMessurier, K. S., Paton, J. C. (2008). Pneumococcal Virulence Gene Expression and Host Cytokine Profiles during Pathogenesis of Invasive Disease. Infect. Immun. 76: 646-657 [Abstract] [Full Text]  
  • Gauthier, J.-F., Fortin, A., Bergeron, Y., Dumas, M.-C., Champagne, M.-E., Bergeron, M. G. (2007). Differential Contribution of Bacterial N-Formyl-Methionyl-Leucyl- Phenylalanine and Host-Derived CXC Chemokines to Neutrophil Infiltration into Pulmonary Alveoli during Murine Pneumococcal Pneumonia. Infect. Immun. 75: 5361-5367 [Abstract] [Full Text]  
  • Luna, C. M., Baquero, S., Gando, S., Patron, J. R., Morato, J. G., Sibila, O., Absi, R., Famiglietti, A., Vay, C. A., Von Stecher, F., Agusti, C., Torres, A. (2007). Experimental Severe Pseudomonas aeruginosa Pneumonia and Antibiotic Therapy in Piglets Receiving Mechanical Ventilation. Chest 132: 523-531 [Abstract] [Full Text]  
  • Petty, J. M., Sueblinvong, V., Lenox, C. C., Jones, C. C., Cosgrove, G. P., Cool, C. D., Rai, P. R., Brown, K. K., Weiss, D. J., Poynter, M. E., Suratt, B. T. (2007). Pulmonary Stromal-Derived Factor-1 Expression and Effect on Neutrophil Recruitment during Acute Lung Injury. J. Immunol. 178: 8148-8157 [Abstract] [Full Text]  
  • Tu, L. N., Jeong, H.-Y., Kwon, H.-Y., Ogunniyi, A. D., Paton, J. C., Pyo, S.-N., Rhee, D.-K. (2007). Modulation of Adherence, Invasion, and Tumor Necrosis Factor Alpha Secretion during the Early Stages of Infection by Streptococcus pneumoniae ClpL. Infect. Immun. 75: 2996-3005 [Abstract] [Full Text]  
  • Ogunniyi, A. D., LeMessurier, K. S., Graham, R. M. A., Watt, J. M., Briles, D. E., Stroeher, U. H., Paton, J. C. (2007). Contributions of Pneumolysin, Pneumococcal Surface Protein A (PspA), and PspC to Pathogenicity of Streptococcus pneumoniae D39 in a Mouse Model. Infect. Immun. 75: 1843-1851 [Abstract] [Full Text]  
  • Marks, M., Burns, T., Abadi, M., Seyoum, B., Thornton, J., Tuomanen, E., Pirofski, L.-a. (2007). Influence of Neutropenia on the Course of Serotype 8 Pneumococcal Pneumonia in Mice. Infect. Immun. 75: 1586-1597 [Abstract] [Full Text]  
  • Graham, R. M. A., Paton, J. C. (2006). Differential Role of CbpA and PspA in Modulation of In Vitro CXC Chemokine Responses of Respiratory Epithelial Cells to Infection with Streptococcus pneumoniae. Infect. Immun. 74: 6739-6749 [Abstract] [Full Text]  
  • Marriott, H. M., Hellewell, P. G., Cross, S. S., Ince, P. G., Whyte, M. K. B., Dockrell, D. H. (2006). Decreased Alveolar Macrophage Apoptosis Is Associated with Increased Pulmonary Inflammation in a Murine Model of Pneumococcal Pneumonia. J. Immunol. 177: 6480-6488 [Abstract] [Full Text]  
  • McCullers, J. A. (2006). Insights into the Interaction between Influenza Virus and Pneumococcus. Clin. Microbiol. Rev. 19: 571-582 [Abstract] [Full Text]  
  • Morona, J. K., Morona, R., Paton, J. C. (2006). Attachment of capsular polysaccharide to the cell wall of Streptococcus pneumoniae type 2 is required for invasive disease. Proc. Natl. Acad. Sci. USA 103: 8505-8510 [Abstract] [Full Text]  
  • Burns, T., Abadi, M., Pirofski, L.-a. (2005). Modulation of the Lung Inflammatory Response to Serotype 8 Pneumococcal Infection by a Human Immunoglobulin M Monoclonal Antibody to Serotype 8 Capsular Polysaccharide. Infect. Immun. 73: 4530-4538 [Abstract] [Full Text]  
  • Kerr, A. R., Paterson, G. K., Riboldi-Tunnicliffe, A., Mitchell, T. J. (2005). Innate Immune Defense against Pneumococcal Pneumonia Requires Pulmonary Complement Component C3. Infect. Immun. 73: 4245-4252 [Abstract] [Full Text]  
  • Villena, J., Racedo, S., Aguero, G., Bru, E., Medina, M., Alvarez, S. (2005). Lactobacillus casei Improves Resistance to Pneumococcal Respiratory Infection in Malnourished Mice. J. Nutr. 135: 1462-1469 [Abstract] [Full Text]  
  • Wang, E., Bergeron, Y., Bergeron, M. G. (2005). Ceftriaxone pharmacokinetics in interleukin-10-treated murine pneumococcal pneumonia. J Antimicrob Chemother 55: 721-726 [Abstract] [Full Text]  
  • Swain, S. D., Wright, T. W., Degel, P. M., Gigliotti, F., Harmsen, A. G. (2004). Neither Neutrophils nor Reactive Oxygen Species Contribute to Tissue Damage during Pneumocystis Pneumonia in Mice. Infect. Immun. 72: 5722-5732 [Abstract] [Full Text]  
  • Garcia-Suarez, M. d. M., Cima-Cabal, M. D., Florez, N., Garcia, P., Cernuda-Cernuda, R., Astudillo, A., Vazquez, F., De Los Toyos, J. R., Mendez, F. J. (2004). Protection against Pneumococcal Pneumonia in Mice by Monoclonal Antibodies to Pneumolysin. Infect. Immun. 72: 4534-4540 [Abstract] [Full Text]  
  • Goto, Y., Hogg, J. C., Whalen, B., Shih, C.-H., Ishii, H., van Eeden, S. F. (2004). Monocyte Recruitment into the Lungs in Pneumococcal Pneumonia. Am. J. Respir. Cell Mol. Bio. 30: 620-626 [Abstract] [Full Text]  
  • Preston, J.A., Beagley, K.W., Gibson, P.G., Hansbro, P.M. (2004). Genetic background affects susceptibility in nonfatal pneumococcal bronchopneumonia. Eur Respir J 23: 224-231 [Abstract] [Full Text]  
  • Dagenais, A., Frechette, R., Yamagata, Y., Yamagata, T., Carmel, J.-F., Clermont, M.-E., Brochiero, E., Masse, C., Berthiaume, Y. (2004). Downregulation of ENaC activity and expression by TNF-{alpha} in alveolar epithelial cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 286: L301-L311 [Abstract] [Full Text]  
  • Blue, C. E., Paterson, G. K., Kerr, A. R., Berge, M., Claverys, J. P., Mitchell, T. J. (2003). ZmpB, a Novel Virulence Factor of Streptococcus pneumoniae That Induces Tumor Necrosis Factor Alpha Production in the Respiratory Tract. Infect. Immun. 71: 4925-4935 [Abstract] [Full Text]  
  • Goto, Y., Hogg, J. C., Suwa, T., Quinlan, K. B., van Eeden, S. F. (2003). A novel method to quantify the turnover and release of monocytes from the bone marrow using the thymidine analog 5'-bromo-2'-deoxyuridine. Am. J. Physiol. Cell Physiol. 285: C253-C259 [Abstract] [Full Text]  
  • Zwijnenburg, P. J. G., van der Poll, T., Florquin, S., Roord, J. J., van Furth, A. M. (2003). IL-1 Receptor Type 1 Gene-Deficient Mice Demonstrate an Impaired Host Defense Against Pneumococcal Meningitis. J. Immunol. 170: 4724-4730 [Abstract] [Full Text]  
  • CANT, A.J., GORDON, S.B., READ, R.C., HART, C.A., WINSTANLEY, C. (2002). Respiratory infections: Proceedings of the Eighth Liverpool Tropical School Bayer Symposium of Microbial Disease held on 3 February 2001. J Med Microbiol 51: 903-914 [Full Text]  
  • Wang, E., Simard, M., Ouellet, N., Bergeron, Y., Beauchamp, D., Bergeron, M. G. (2002). Pathogenesis of Pneumococcal Pneumonia in Cyclophosphamide-Induced Leukopenia in Mice. Infect. Immun. 70: 4226-4238 [Abstract] [Full Text]  
  • Gordon, S B, Read, R C (2002). Macrophage defences against respiratory tract infections: The immunology of childhood respiratory infections. Br Med Bull 61: 45-61 [Abstract] [Full Text]  
  • Sato, S., Ouellet, N., Pelletier, I., Simard, M., Rancourt, A., Bergeron, M. G. (2002). Role of Galectin-3 as an Adhesion Molecule for Neutrophil Extravasation During Streptococcal Pneumonia. J. Immunol. 168: 1813-1822 [Abstract] [Full Text]  
  • Wang, E., Ouellet, N., Simard, M., Fillion, I., Bergeron, Y., Beauchamp, D., Bergeron, M. G. (2001). Pulmonary and Systemic Host Response to Streptococcus pneumoniae and Klebsiella pneumoniae Bacteremia in Normal and Immunosuppressed Mice. Infect. Immun. 69: 5294-5304 [Abstract] [Full Text]  
  • Fillion, I., Ouellet, N., Simard, M., Bergeron, Y., Sato, S., Bergeron, M. G. (2001). Role of Chemokines and Formyl Peptides in Pneumococcal Pneumonia-Induced Monocyte/Macrophage Recruitment. J. Immunol. 166: 7353-7361 [Abstract] [Full Text]  
  • Duong, M., Simard, M., Bergeron, Y., Bergeron, M. G. (2001). Kinetic Study of the Inflammatory Response in Streptococcus pneumoniae Experimental Pneumonia Treated with the Ketolide HMR 3004. Antimicrob. Agents Chemother. 45: 252-262 [Abstract] [Full Text]  
  • Gingles, N. A., Alexander, J. E., Kadioglu, A., Andrew, P. W., Kerr, A., Mitchell, T. J., Hopes, E., Denny, P., Brown, S., Jones, H. B., Little, S., Booth, G. C., McPheat, W. L. (2001). Role of Genetic Resistance in Invasive Pneumococcal Infection: Identification and Study of Susceptibility and Resistance in Inbred Mouse Strains. Infect. Immun. 69: 426-434 [Abstract] [Full Text]  
  • GILLESPIE, S.H., BALAKRISHNAN, I. (2000). Pathogenesis of pneumococcal infection. J Med Microbiol 49: 1057-1067 [Abstract] [Full Text]  
  • Chen, G. H., Reddy, R. C., Newstead, M. W., Tateda, K., Kyasapura, B. L., Standiford, T. J. (2000). Intrapulmonary TNF Gene Therapy Reverses Sepsis-Induced Suppression of Lung Antibacterial Host Defense. J. Immunol. 165: 6496-6503 [Abstract] [Full Text]  
  • Chroneos, Z. C., Wert, S. E., Livingston, J. L., Hassett, D. J., Whitsett, J. A. (2000). Role of Cystic Fibrosis Transmembrane Conductance Regulator in Pulmonary Clearance of Pseudomonas aeruginosa In Vivo. J. Immunol. 165: 3941-3950 [Abstract] [Full Text]  
  • Wang, E., Simard, M., Bergeron, Y., Beauchamp, D., Bergeron, M. G. (2000). In Vivo Activity and Pharmacokinetics of Ziracin (SCH27899), a New Long-Acting Everninomicin Antibiotic, in a Murine Model of Penicillin-Susceptible or Penicillin-Resistant Pneumococcal Pneumonia. Antimicrob. Agents Chemother. 44: 1010-1018 [Abstract] [Full Text]  
  • Kadioglu, A., Gingles, N. A., Grattan, K., Kerr, A., Mitchell, T. J., Andrew, P. W. (2000). Host Cellular Immune Response to Pneumococcal Lung Infection in Mice. Infect. Immun. 68: 492-501 [Abstract] [Full Text]  
  • Bergeron, Y., Ouellet, N., Simard, M., Olivier, M., Bergeron, M. G. (1999). Immunomodulation of Pneumococcal Pulmonary Infection with NG-Monomethyl-L-Arginine. Antimicrob. Agents Chemother. 43: 2283-2290 [Abstract] [Full Text]  
  • Bergeron, Y., Deslauriers, A.-M., Ouellet, N., Gauthier, M.-C., Bergeron, M. G. (1999). Influence of Cefodizime on Pulmonary Inflammatory Response to Heat-Killed Klebsiella pneumoniae in Mice. Antimicrob. Agents Chemother. 43: 2291-2294 [Abstract] [Full Text]  
  • Duong, M., Simard, M., Bergeron, Y., Ouellet, N., Côté-Richer, M., Bergeron, M. G. (1998). Immunomodulating Effects of HMR 3004 on Pulmonary Inflammation Caused by Heat-Killed Streptococcus pneumoniae in Mice. Antimicrob. Agents Chemother. 42: 3309-3312 [Abstract] [Full Text]  
  • Bergeron, Y., Ouellet, N., Deslauriers, A.-M., Simard, M., Olivier, M., Bergeron, M. G. (1998). Reduction by Cefodizime of the Pulmonary Inflammatory Response Induced by Heat-Killed Streptococcus pneumoniae in Mice. Antimicrob. Agents Chemother. 42: 2527-2533 [Abstract] [Full Text]  
  • Ichinose, F., Zapol, W. M., Sapirstein, A., Ullrich, R., Tager, A. M., Coggins, K., Jones, R., Bloch, K. D. (2001). Attenuation of Hypoxic Pulmonary Vasoconstriction by Endotoxemia Requires 5-Lipoxygenase in Mice. Circ. Res. 88: 832-838 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»