Establishment of aStreptococcus pneumoniaenasopharyngeal colonization model in adult mice

Wu, Hong-Yin; Virolainen, Anni; Mathews, B.; King, Janice; Russell, Michael W.; Briles, David E.

doi:10.1006/mpat.1997.0142

Cited by 107 publications

(146 citation statements)

References 34 publications

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“…Previous work by Moreno et al has shown that carriage of sp14 was consistent for 3-10 weeks in their model, and that colonized mice harbored 5 × 10 3 cfu of S. pneumoniae [20]. Our results are consistent with their findings, as well as with Wu et al who demonstrated that sp14 carriage is stable for over 2 weeks and colonized mice contained 10 3 -10 4 cfu of sp14 [17]. Based on these results, we colonized mice with sp14 and allowed them to clear colonization before they were sacrificed for adoptive transfer studies.…”

Section: Discussionsupporting

confidence: 93%

“…In contrast, sp19F was able to maintain colonization throughout the entire study (figure 1). Previous studies have shown that pneumococci maintain colonization at levels between 10 2 and 10 4 cfu per mouse [17]. Based on these results, we utilized sp14 for the duration of our studies as colonization and clearance were each confirmed.…”

Section: Duration Of Streptococcal Colonizationmentioning

confidence: 99%

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B cell mediated priming following pneumococcal colonization

Rabquer

Shriner

Smithson

et al. 2007

Vaccine

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The primary reservoir for Streptococcus pneumoniae is the human nasopharynx, and colonization is often the initial step in pathogenesis. Recently we have demonstrated that pneumococcal colonization primes the immune response to subsequent vaccination with the pneumococcal conjugate vaccine (CPV). In this study we wished to determine if colonization stimulates the production of B cell memory that is activated following vaccination with CPV. To test this hypothesis, we colonized mice with S. pneumoniae serotype 14, adoptively transferred their B cells and CD4 + T cells into naïve recipients, and vaccinated the recipients with CPV. Our results indicate that pneumococcal colonization stimulates the production of memory B cells which are responsible for enhancing the immune response to CPV vaccination.

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Section: Discussionsupporting

confidence: 93%

Section: Duration Of Streptococcal Colonizationmentioning

confidence: 99%

B cell mediated priming following pneumococcal colonization

Rabquer

Shriner

Smithson

et al. 2007

Vaccine

View full text Add to dashboard Cite

show abstract

“…We suspect that GLS on human cells are involved in the bacterial attachment at these sites, probably through interactions with the C-polysaccharides of the pneumococcus. Several previous studies (12,14,16,32) have clearly shown that interactions between GLS and Cpolysaccharides occur in vitro. Although our studies do not rule out a role for the platelet-activating factor receptor, they suggest that it may not be a primary event in the initial in vivo infections.…”

Section: Discussionmentioning

confidence: 92%

“…A second major observation of this study is that host defense of the brain is active and effective because rapidly progressing brain disease was not observed even after pneumococci entered the OB and brain. Moreover, large numbers of mice have been used in carriage models over the years without the mice commonly giving symptoms of meningitis, paralysis, or death (32,33).…”

Section: Discussionmentioning

confidence: 99%

Pneumococcal carriage results in ganglioside-mediated olfactory tissue infection

Ginkel

McGhee

Watt

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Streptococcus pneumoniae cause considerable morbidity and mortality, with persistent neurological sequelae, particularly in young children and the elderly. It is widely assumed that carriage occurs through direct mucosal colonization from the environment whereas meningitis results from invasion from the blood. However, the results of published studies can be interpreted that pneumococci may enter the brain directly from the nasal cavity by axonal transport through olfactory nerves. This hypothesis is based on findings that (i) teichoic acid of the pneumococcal cell wall interact with gangliosides (GLS), (ii) the interaction of GLS with cholera toxin leads to axonal transport through the olfactory nerves into the brain, and (iii) viruses enter the brain through axonal transport into olfactory nerves. After nasal inoculation, we observe high numbers of pneumococci in nasal washes and the olfactory nerves and epithelium. Significant numbers of pneumococci also infected the olfactory bulbs, brain, and the trigeminal ganglia. The absence of bacteremia in this model makes it unlikely that the bacteria entered the brain from the blood stream. Recovery of colony-forming units from the brain, lungs, olfactory nerves, and epithelium and nasal washes was inhibited by incubating pneumococci with GLS before nasal inoculation. These findings, confirmed by PCR and immunohistochemistry, support a GLSmediated process of infection and are consistent with pneumococci reaching the brain through retrograde axonal transport.

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“…Therefore, 72 h was chosen as the end-point of infection in this work, in order to maximize the number of pneumococci recovered from the tissues. At this time-point, eight mice were sacrificed by CO 2 asphyxiation, and nasopharyngeal washes, and lung and blood samples were collected using an adaptation of the protocol described by Wu et al (1997). Briefly, the nasopharynx of each mouse was washed with 1 ml 0?5 % trypsin solution in PBS, and the washings were placed on ice until further use.…”

Section: Methodsmentioning

confidence: 99%

Differential expression of key pneumococcal virulence genes in vivo

2006

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Few studies have examined in vivo virulence gene expression in Streptococcus pneumoniae. In this study, expression of key pneumococcal virulence genes cbpA, pspA, ply, psaA, cps2A, piaA, nanA and spxB in the nasopharynx, lungs and bloodstream of mice was investigated, following intranasal challenge with the serotype 2 strain D39. Bacterial RNA was extracted, linearly amplified and assayed by real-time RT-PCR. At 72 h, cbpA mRNA was present at higher levels in the nasopharynx and lungs than in the blood. At this time-point, the mRNAs for PspA and PiaA were most abundant in the nasopharynx, whereas no significant difference in gene expression between niches was observed for ply, psaA and cps2A. Both nanA and spxB mRNAs were present in higher amounts in the nasopharynx than in the lungs or blood. These findings illustrate the dynamic nature of pneumococcal virulence gene expression in vivo. INTRODUCTIONStreptococcus pneumoniae (the pneumococcus) is a globally significant pathogen, responsible for invasive diseases such as pneumonia, bacteraemia and meningitis . The pneumococcus asymptomatically colonizes the nasopharynx, and such carriage is considered essential for subsequent development of disease in susceptible individuals (particularly infants, the elderly, and the immunocompromised). Disease commonly occurs following the aspiration of bacteria from the nasopharynx into the lungs, followed by colonization of the pulmonary epithelium and subsequent development of pneumonia. From this niche, the pneumococcus can invade the bloodstream and cause sepsis. Alternatively, bacteraemia can occur, following direct translocation from the nasopharyngeal epithelium into underlying tissues. The gene regulatory mechanisms involved in transition between, and survival in, these distinct host niches are poorly understood. This has primarily been due to technical difficulties in harvesting sufficient quantities of pneumococci from an animal model to perform accurate and quantitative RNA assays, particularly from niches such as the nasopharynx, in which bacteria exist asymptomatically and in low numbers.Several studies have been conducted in recent years comparing in vivo and in vitro pneumococcal gene expression. Orihuela et al. (2000) used Northern blotting to assess virulence gene mRNA levels in type 3 pneumococci grown in sealed dialysis bags implanted in the murine peritoneal cavity. In another study, differences in gene expression between virulent type 2 pneumococci harvested from the blood of mice infected intraperitoneally and those grown in serum broth were examined using semi-quantitative RT-PCR (Ogunniyi et al., 2002). More recently, in vivo studies have used microarray technology to quantitate S. pneumoniae transcript abundance in the blood of infected mice and the cerebrospinal fluid of infected rabbits (Orihuela et al., 2004b).The present work is the first to evaluate in vivo changes in pneumococcal gene expression during the natural progression of disease from colonization of the nasopharynx to invasion of the lungs...

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Establishment of aStreptococcus pneumoniaenasopharyngeal colonization model in adult mice

Cited by 107 publications

References 34 publications

B cell mediated priming following pneumococcal colonization

B cell mediated priming following pneumococcal colonization

Pneumococcal carriage results in ganglioside-mediated olfactory tissue infection

Differential expression of key pneumococcal virulence genes in vivo

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