Streptococcus pneumoniae strain-dependent lung inflammatory responses in a murine model of pneumococcal pneumonia

Mohler, J.; Azoulay-Dupuis, E.; Amory-Rivier, Cécile; Mazoit, Jean Xavier; Bédos, Jean Pierre; Rieux, Véronique; Moine, Pierre

doi:10.1007/s00134-003-1699-x

Cited by 34 publications

(19 citation statements)

References 43 publications

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“…The tissue inflammatory response to pneumococcal pneumonia is a function of the mouse (58) and the pneumococcal strain (52). In our study, the predominantly interstitial inflam- D).…”

Section: Discussionmentioning

confidence: 68%

Influence of Neutropenia on the Course of Serotype 8 Pneumococcal Pneumonia in Mice

et al. 2007

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Polymorphoneutrophils (PMNs) are important effector cells in host defense against pneumonia. However, PMNs can also induce inflammation and tissue damage. To investigate the contribution of PMNs to host defense against pneumococcal pneumonia, we determined the effect of the PMN-depleting rat monoclonal antibody RB6-8C5 (RB6) on survival and inflammatory and cellular response in the lungs to a lethal intranasal infection with a serotype 8 pneumococcus in BALB/c mice. Control mice received rat immunoglobulin G (rIgG). Strikingly, the survival of RB6-treated mice was significantly prolonged compared to that of rIgG-treated mice. Although the numbers of CFU in the lungs were statistically similar in both groups 4, 24, and 32 h after infection, rIgG-treated mice developed higher levels of bacteremia, and histopathological examination of the lungs of infected mice revealed marked differences between RB6-and rIgG-treated mice. RB6-treated mice had focal, perivascular lesions without accompanying parenchymal inflammation, and rIgG-treated mice had diffuse, interstitial parenchymal inflammation. Lung homogenates from the rIgG-treated mice had more leukocytes and significantly more total and apoptotic PMNs as determined by fluorescence-activated cell sorter analysis with Annexin V and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling staining of lung tissue samples. Studies with a pneumolysin-deficient mutant of the serotype 8 strain we used also demonstrated the prolonged survival of RB6-compared to rIgG-treated mice. Taken together, our findings suggest that PMNs enhance the likelihood of early death and alter the pathological response to pneumococcal lung infection in BALB/c mice with serotype 8 pneumonia without significantly affecting bacterial clearance or the cytokine response.

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“…The tissue inflammatory response to pneumococcal pneumonia is a function of the mouse (58) and the pneumococcal strain (52). In our study, the predominantly interstitial inflam- D).…”

Section: Discussionmentioning

confidence: 68%

Influence of Neutropenia on the Course of Serotype 8 Pneumococcal Pneumonia in Mice

et al. 2007

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“…Over 90 serotypes of S. pneumoniae have been characterized to date, all with differing levels of pathogenicity and virulence factor expression, resulting in differential prevalence in the human population [20][21][22][23] . Similarly, in mice, it has been reported that the extent of, and kinetics associated with, the immune response elicited in response to a nasopharyngeal colonization is dependent on the colonizing strain itself 24 . Thus, selection of an appropriate strain to utilize for the establishment of a nasopharyngeal colonization is not a trivial matter, nor is selection of mouse genetic background.…”

Section: Discussionmentioning

confidence: 95%

Characterization of Inflammatory Responses During Intranasal Colonization with <em>Streptococcus pneumoniae</em>

Puchta

Thurn

Bowdish

2014

JoVE

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Nasopharyngeal colonization by Streptococcus pneumoniae is a prerequisite to invasion to the lungs or bloodstream 1 . This organism is capable of colonizing the mucosal surface of the nasopharynx, where it can reside, multiply and eventually overcome host defences to invade to other tissues of the host. Establishment of an infection in the normally lower respiratory tract results in pneumonia. Alternatively, the bacteria can disseminate into the bloodstream causing bacteraemia, which is associated with high mortality rates 2 , or else lead directly to the development of pneumococcal meningitis. Understanding the kinetics of, and immune responses to, nasopharyngeal colonization is an important aspect of S. pneumoniae infection models.Our mouse model of intranasal colonization is adapted from human models 3 and has been used by multiple research groups in the study of host-pathogen responses in the nasopharynx [4][5][6][7] . In the first part of the model, we use a clinical isolate of S. pneumoniae to establish a selflimiting bacterial colonization that is similar to carriage events in human adults. The procedure detailed herein involves preparation of a bacterial inoculum, followed by the establishment of a colonization event through delivery of the inoculum via an intranasal route of administration. Resident macrophages are the predominant cell type in the nasopharynx during the steady state. Typically, there are few lymphocytes present in uninfected mice 8 , however mucosal colonization will lead to low-to high-grade inflammation (depending on the virulence of the bacterial species and strain) that will result in an immune response and the subsequent recruitment of host immune cells. These cells can be isolated by a lavage of the tracheal contents through the nares, and correlated to the density of colonization bacteria to better understand the kinetics of the infection.

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“…The oropharynges were transilluminated, and the tracheas were cannulated with needles attached to microliter syringes containing the pneumococcal suspension (12). This model is still used in several studies on drug efficacy, host response to infection, and the role of pneumococcal virulence factors in the disease (1,11,19,168,169,208,237). Another i.t.…”

Section: Mouse Modelsmentioning

confidence: 99%

Animal Models ofStreptococcus pneumoniaeDisease

2008

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SUMMARY Streptococcus pneumoniae is a colonizer of human nasopharynx, but it is also an important pathogen responsible for high morbidity, high mortality, numerous disabilities, and high health costs throughout the world. Major diseases caused by S. pneumoniae are otitis media, pneumonia, sepsis, and meningitis. Despite the availability of antibiotics and vaccines, pneumococcal infections still have high mortality rates, especially in risk groups. For this reason, there is an exceptionally extensive research effort worldwide to better understand the diseases caused by the pneumococcus, with the aim of developing improved therapeutics and vaccines. Animal experimentation is an essential tool to study the pathogenesis of infectious diseases and test novel drugs and vaccines. This article reviews both historical and innovative laboratory pneumococcal animal models that have vastly added to knowledge of (i) mechanisms of infection, pathogenesis, and immunity; (ii) efficacies of antimicrobials; and (iii) screening of vaccine candidates. A comprehensive description of the techniques applied to induce disease is provided, the advantages and limitations of mouse, rat, and rabbit models used to mimic pneumonia, sepsis, and meningitis are discussed, and a section on otitis media models is also included. The choice of appropriate animal models for in vivo studies is a key element for improved understanding of pneumococcal disease.

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Streptococcus pneumoniae strain-dependent lung inflammatory responses in a murine model of pneumococcal pneumonia

Cited by 34 publications

References 43 publications

Influence of Neutropenia on the Course of Serotype 8 Pneumococcal Pneumonia in Mice

Influence of Neutropenia on the Course of Serotype 8 Pneumococcal Pneumonia in Mice

Characterization of Inflammatory Responses During Intranasal Colonization with <em>Streptococcus pneumoniae</em>

Animal Models ofStreptococcus pneumoniaeDisease

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