Pneumocystis carinii infection in young non-immunosuppressed rabbits. Kinetics of infection and of the primary specific immune response

Tamburrini, Enrica; Ortona, Elena; Visconti, Elena; Mencarini, Paola; Margutti, Paola; Zolfo, María; Barca, Stefano; Peters, Sarah; Wakefield, Ann E.; Siracusano, Alessandra

doi:10.1007/s004300050098

Cited by 18 publications

(12 citation statements)

References 29 publications

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“…It seems unlikely that in nature, the number of immunodeficient hosts is adequate to perpetuate this organism. It has already been shown that immunocompetent infant animals can acquire Pneumocystis from infected mothers (3,7,15,23) and that the organisms persist for several weeks. In addition, recent work by others has shown that immunocompetent mice can transmit P. carinii f. sp.…”

Section: Vol 71 2003 Pneumocystis Infection In Cohoused Mice 2069mentioning

confidence: 99%

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Exposure of Immunocompetent Adult Mice to Pneumocystis carinii f. sp. muris by Cohousing: Growth of P . carinii f. sp. muris and Host Immune Response

Gigliotti

Harmsen

2003

Infect Immun

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There has been emerging evidence that immunocompetent hosts can harbor Pneumocystis in their lungs. The purpose of this study was to determine the kinetics of Pneumocystis carinii f. sp. muris infection in adult immunocompetent mice and the host immune response to the organisms. To accomplish this, we exposed adult immunocompetent mice to SCID mice infected with P. carinii f. sp. muris by cohousing. We found that P. carinii f. sp. muris was detectable in the lungs of cohoused immunocompetent mice by PCR by 3 weeks after the beginning of cohousing. At about 4 weeks of cohousing, P. carinii f. sp. muris was readily detectable in the lungs of mice by microscopic techniques. Also at this time, P. carinii f. sp. muris-specific immunoglobulin G was found in the sera of the mice, and CD62low CD4- and CD8-positve T cells accumulated in the lungs. Shortly after this immune response, the P. carinii f. sp. muris organisms were cleared from the lungs. Adult mice cohoused for only 1 week also contained P. carinii f. sp. muris cysts detectable by silver staining at 5 and 6 weeks after the beginning of cohousing. We also found that the P. carinii f. sp. muris organisms grew to greater numbers in the lungs of BALB/c mice than in those of C57BL6 mice. This indicates that immunocompetent hosts develop a mild infection with P. carinii f. sp. muris which resolves in 5 to 6 weeks when there is a detectable immune response to the organism. Once an acquired immune response was initiated, the P. carinii f. sp. muris organisms were quickly eliminated without clinical signs of disease

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Section: Vol 71 2003 Pneumocystis Infection In Cohoused Mice 2069mentioning

confidence: 99%

“…Recent studies suggest that children may frequently harbor Pneumocystis in their lungs (17,24,26), and animal experiments have shown that neonatal mice, pigs, and rabbits can harbor substantial numbers of Pneumocystis organisms (3,7,15,23). However, after intratracheal instillation of Pneumocystis carinii f. sp.…”

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confidence: 99%

Exposure of Immunocompetent Adult Mice to Pneumocystis carinii f. sp. muris by Cohousing: Growth of P . carinii f. sp. muris and Host Immune Response

Gigliotti

Harmsen

2003

Infect Immun

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“…Nonimmunosuppressed young rabbits routinely develop microscopically detectable infections with Pneumocystis early after birth that can reach burdens in the millions of organisms (26,28). The infection is gradually resolved as the immune system matures.…”

Section: Vol 1 2002 Early Acquisition Of P Carinii In Rats 417mentioning

confidence: 99%

“…The ability to detect P. carinii DNA in oral swab samples represents a significant technical breakthrough that can be used to increase our understanding of the life cycle of P. carinii in an antemortem setting. Sampling of the oral cavity and PCR detection of Pneumocystis have now been authenticated as a means to determine Pneumocystis exposure in two mammalian hosts, rats and humans, in both immunosuppressed and nonimmunosuppressed states (7,10,12,18,28,31). Besides the obvious diagnostic application, this technique provides an experimental tool that can be used for selection of rats exposed to P. carinii prior to induction into an experiment, so that investigators need not wait to discover the presence of the organism in control animals after 8 to 12 weeks of immunosuppression.…”

Section: Vol 1 2002 Early Acquisition Of P Carinii In Rats 417mentioning

confidence: 99%

Early Acquisition of Pneumocystis carinii in Neonatal Rats as Evidenced by PCR and Oral Swabs

et al. 2002

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The complete life cycle of Pneumocystis carinii has not been defined, but accumulating evidence suggests that the mammalian host may acquire this organism early in life. In the present study, the initial time of P. carinii acquisition was determined in rats by amplification of P. carinii DNA in oral swabs from seven sets of pups and dams and from fetal tissue obtained by cesarean section of three gravid female rats. DNA extracted from all samples was amplified by using PCR primers directed to the P. carinii mitochondrial large subunit rRNA. Amplicons were produced from 80% (28 of 35) of pups within 2 h after birth; from 97% (34 of 35) after 24 h, and in all of the serially sampled pups by 48 h. No P. carinii amplicons were produced from 48 fetuses or their placentae taken by cesarean section. Thus, P. carinii is acquired almost immediately after birth, and placental transmission occurs rarely, if ever, in rats.

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“…Presently, evidence that primary PCP is caused by reinfection rather than reactivation is based on animal experiments, in which primary infection is completely cleared (27,32), and autopsy studies, in which P. carinii DNA is not detected in immunocompetent adults (25). However, whether reactivation or reinfection causes recurrent PCP in HIV-infected patients may be more complex.…”

mentioning

confidence: 99%

Heterogeneity and Compartmentalization of Pneumocystis carinii f. sp. hominis Genotypes in Autopsy Lungs

Helweg‐Larsen

Lundgren

2001

J Clin Microbiol

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The extent and importance of genotype heterogeneity of Pneumocystis carinii f. sp. hominis within lungs have not previously been investigated. Two hundred forty PCR clones obtained from respiratory specimens and lung segments from three patients with fatal P. carinii pneumonia were investigated to detect genetic diversity in the internal transcribed spacer (ITS) region of the nuclear rRNA operon, the mitochondrial large-subunit (mtLSU) rRNA gene, and the dihydropteroate synthase-encoding gene. For two of the three examined patients, a mixture of different mtLSU rRNA and ITS genotypes was observed. Not all genotypes present in the lungs at autopsy were detected in the diagnostic respiratory samples. Compartmentalization of specific ITS and mtLSU rRNA sequence types was observed in different lung segments. In conclusion, the interpretation of genotype data and in particular ITS sequence types in the assessment of epidemiological questions should be cautious since genotyping done on respiratory samples cannot a priori be assumed to represent all genotypes present within the lung.The interpretation of molecular typing results in epidemiological studies of Pneumocystis carinii is complicated by the existence of coinfections. Several studies have reported coinfection with more than one genotype present in specimens from single patients (5). However, the majority of studies have relied on DNA extraction from diagnostic respiratory samples, which yield only a limited number of organisms. Very little is known of the dynamics of genotypes within the lungs, and whether genotype variation could result from compartmentalization of genotypes within the lungs has not previously been investigated.To address these questions, we studied polymorphisms at three genetic loci by a detailed investigation of DNA obtained from different segments of autopsy lungs. The mitochondrial large-subunit (mtLSU) rRNA and internal transcribed spacer (ITS) loci were chosen for analysis since these genes are genes most frequently used for genotype analysis and the dihydropteroate synthase (DHPS) locus, the target of sulfone and sulfonamide drugs, was chosen because of its association with sulfa resistance (9, 16).Specimens were obtained at diagnosis and postmortem from three patients who died of P. carinii pneumonia (PCP) between 1994 and 1997. PCP was diagnosed by microscopy and confirmed by histology at autopsy. Two patients with AIDS were included. Patient AIDS-1 was a 56-year-old male who died after 3 days of therapy, and patient AIDS-2 was a 45-year-old male who died after 17 days of therapy. Patient HL (age, 31 years) had a recurrence of Hodgkin's lymphoma and died 14 days after diagnosis of PCP.After autopsy the whole right lungs from patients AIDS-1 and AIDS-2 were stored at Ϫ80°C. After thawing, five biopsies were cut from five different areas of each lung. Two-by three-cm biopsies were selected from the apex and from the superficial and central areas of the middle lobe and from the base and central part of the inferior lobe of the right lu...

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Pneumocystis carinii infection in young non-immunosuppressed rabbits. Kinetics of infection and of the primary specific immune response

Cited by 18 publications

References 29 publications

Exposure of Immunocompetent Adult Mice to Pneumocystis carinii f. sp. muris by Cohousing: Growth of P . carinii f. sp. muris and Host Immune Response

Exposure of Immunocompetent Adult Mice to Pneumocystis carinii f. sp. muris by Cohousing: Growth of P . carinii f. sp. muris and Host Immune Response

Early Acquisition of Pneumocystis carinii in Neonatal Rats as Evidenced by PCR and Oral Swabs

Heterogeneity and Compartmentalization of Pneumocystis carinii f. sp. hominis Genotypes in Autopsy Lungs

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