Recovery from Pneumocystis carinii pneumonia in dexamethasone-treated Wistar rats (original) (raw)
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International Journal of Experimental Pathology
The development and resolution of naturally-acquired Pneumocystis carinii pneumonia was studied in a severe combined immunodefncient (SCID) mouse model by light and electron microscopies. Initial infection was evident in 3-week-old SCID mice and started as focal alveolar colonization in the areas near terminal airways. Pronounced pulmonary inflammation occurred in animals of 10 weeks or older and the infection intensity reached a plateau in animals 12 weeks of age. At this stage of disease, the histopathological features of P. carinii infection in SCID mice were similar to those of immunodeficient man. Reconstitution of SCID mice with immunocompetent spleen cells at day 0 induced substantial pulmonary inflammation that was evident already by day 7 and most severe and extensive by day 12. The clearance of P. carinii did not begin until after day 12 and was almost completed by day 1 7. Alveolar macrophages in mice killed between days 12 and 1 5, at the time when P. carinii are being rapidly cleared, appeared active but phagocytosis of P. carinii was not commonly observed by either light or electron microscopy. These results suggest that (1) the presence of non-lymphoid inflammatory cells in SCID mice is not sufficient to control P. carinii infection;
Experimental Pneumocystis carinii pneumonia in the ferret
PubMed, 1987
Pneumocystis carinii pneumonia (PCP) was provoked in the ferret, Mustela pulorius furo, by immunosuppression with daily long-term administration of cortisone acetate, 10-20 mg/kg subcutaneously for 9 to 10 weeks, Microscopically P. carinii was observed in the lungs of all 11 treated animals: mild to moderate in five and extensive disease in six. The histopathological features of PCP in the ferret included interstitial pneumonitis, scant mononuclear cell alveolitis, with abundant cysts and trophozoites visible in a focal distribution. There were few neutrophils present. Electron microscopy showed large numbers of both cysts and trophozoites in close association with type I cells. No bacterial pathogens were isolated from the lungs of immunosuppressed animals but an unexplained eosinophilic enteritis was present in treated animals. P carinii pneumonia developed without significant body weight loss during corticosteroid administration, unlike previously described studies using corticosteroid-treated rodents. Ferrets thus appear to be a 'steroid resistant' animal, like man, and therefore a more suitable model for immunological studies of host response to PCP than rodents. This new model also has practical advantages over previously described animal models of PCP, including larger lung and airway size.
PLoS ONE, 2013
To better understand the role of immunocompetent hosts in the diffusion of Pneumocystis in the environment, airborne shedding of Pneumocystis carinii in the surrounding air of experimentally infected Sprague Dawley rats was quantified by means of a real-time PCR assay, in parallel with the kinetics of P. carinii loads in lungs and specific serum antibody titres. Pneumocystis-free Sprague Dawley rats were intratracheally inoculated at day 0 (d0) and then followed for 60 days. P. carinii DNA was detected in lungs until d29 in two separate experiments and thereafter remained undetectable. A transient air excretion of Pneumocystis DNA was observed between d14 and d22 in the first experiment and between d9 and d19 in the second experiment; it was related to the peak of infection in lungs. IgM and IgG anti-P. carinii antibody increase preceded clearance of P. carinii in the lungs and cessation of airborne excretion. In rats receiving a second challenge 3 months after the first inoculation, Pneumocystis was only detected at a low level in the lungs of 2 of 3 rats at d2 post challenge and was never detected in air samples. Anti-Pneumocystis antibody determinations showed a typical secondary IgG antibody response. This study provides the first direct evidence that immunocompetent hosts can excrete Pneumocystis following a primary acquired infection. Lung infection was apparently controlled by the immune response since fungal burdens decreased to become undetectable as specific antibodies reached high titres in serum. This immune response was apparently protective against reinfection 3 months later.
Immunohistochemical study of the cellular immune response in human Pneumocystis carinii pneumonia
Jornal Brasileiro de Patologia e Medicina Laboratorial, 2006
Objectives: It has been experimentally demonstrated that host defense against Pneumocystis carinii depends on complex interactions within host immune response, mainly CD4 lymphocytes and alveolar macrophages. Since this is an important agent related to immunodeficiency, our purpose was to characterize the inflammatory immune response in lung from necropsy of AIDS patients. Procedures: Twenty-five necropsies with diagnosis of Pneumocystis carinii pneumonia were selected for immunohistochemical investigation of CD4 and CD8 lymphocytes, macrophages (CD68+), NK cells (CD57+) and cells expressing TNF-alpha. The immunostained cells were quantified and statistically analyzed. Results: All specimens presented a great number of cysts of Pneumocystis carinii in alveoli, as well as septal enlargement with inflammatory infiltrate constituted predominantly by lymphocytes and macrophages. CD4+ T cells were decreased in number, and CD8+ T cells, NK cells and macrophages predominated. Cells expressing TNF-alpha were frequently observed in septal inflammatory infiltrate. Conclusions: The immunosupression related to AIDS induces a reduction in the number of CD4+ T cells and influences high-level parasitism. The cell components that characterize the inflammatory infiltrate contribute to the severe lung injury of those patients. Pneumocystis carinii Immunohistochemistry Cellular immune response Pneumocystis carinii Imuno-histoquímica Resposta imune celular Primeira submissão em 18/10/04 Última submissão em 18/01/06 Aceito para publicação em 01/02/06 Publicado em 20/02/06
Veterinary Pathology, 2012
A prevalent and distinctive infectious interstitial pneumonia (IIP) of immunocompetent laboratory rats was suspected to be caused by a putative virus, termed rat respiratory virus, but this was never substantiated. To study this disease, 2 isolators were independently populated with rats from colonies with endemic disease, which was perpetuated by the regular addition of naive rats. After Pneumocystis was demonstrated by histopathology and polymerase chain reaction (PCR) in the lungs of rats from both isolators and an earlier bedding transmission study, the relationship between Pneumocystis and IIP was explored further by analyzing specimens from 3 contact transmission experiments, diagnostic submissions, and barrier room breeding colonies, including 1 with and 49 without IIP. Quantitative (q) PCR and immunofluorescence assay only detected Pneumocystis infection and serum antibodies in rats from experiments or colonies in which IIP was diagnosed by histopathology. In immunocompetent hosts, the Pneumocystis concentration in lungs corresponded to the severity and prevalence of IIP; seroconversion occurred when IIP developed and was followed by the concurrent clearance of Pneumocystis from lungs and resolution of disease. Experimentally infected immunodeficient RNU rats, by contrast, did not seroconvert to Pneumocystis or recover from infection. qPCR found Pneumocystis at significantly higher concentrations and much more often in lungs than in bronchial and nasal washes and failed to detect Pneumocystis in oral swabs. The sequences of a mitochondrial ribosomal large-subunit gene region for Pneumocystis from 11 distinct IIP sources were all identical to that of P. carinii. These data provide substantial evidence that P. carinii causes IIP in immunocompetent rats.
Antibody to Pneumocystis carinii Protects Rats and Mice from Developing Pneumonia
Clinical and diagnostic laboratory immunology, 1998
Well-proven mouse and rat models were used to show that polyclonal antisera to Pneumocystis carinii protect against P. carinii pneumonia. Antibodies were obtained from animals that were allowed to recover from severe P. carinii pneumonia after immunosuppression had been stopped and which then were given a booster injection of P. carinii from the same animal species. Mice immunosuppressed with corticosteroids or antibodies to L3T4 ؉ lymphocytes (which are comparable to CD4 cells of humans) and transtracheally inoculated with mouse P. carinii did not develop P. carinii pneumonia if they were passively immunized with antiserum, while mice immunosuppressed and inoculated by identical procedures but not given antibodies developed severe infections. Rats immunosuppressed with corticosteroids and inoculated with rat P. carinii had less severe infections if they were given rat anti-P. carinii antisera. The polyclonal antisera developed in mice provided greater protection for the mice than the polyclonal rat antisera did for the rats; however, the potencies and compositions of the antisera were not quantitated and probably differed. Since both rats and mice can be protected from P. carinii infections with polyclonal antisera, it may be possible to develop vaccines that will elicit protective antibodies in humans.
Journal of Clinical Investigation, 1999
The clinical severity of Pneumocystis carinii pneumonia (PCP) correlates closely with the appearance of pulmonary markers of inflammation. Therefore, a model system was developed whereby physiological studies could be performed on live mice to determine the extent to which pulmonary inflammation contributes to respiratory impairment during PCP. P. carinii-infected severe combined immunodeficient mice displayed little evidence of pulmonary inflammation and exhibited normal oxygenation and dynamic lung compliance. When comparably infected littermates were immunologically reconstituted, however, an intense immune-mediated inflammatory response was observed that resulted in significant decreases in both lung compliance and oxygenation. As the pneumonia resolved, pulmonary function returned toward normal. To begin to define the cell populations contributing to inflammation-associated respiratory impairment during PCP, similar studies were performed in CD4 + T cell-depleted mice. Mice depleted of both CD4 + and CD8 + cells developed infection, but they demonstrated neither abnormal lung compliance nor increased respiratory rate and displayed no markers of lung injury. In contrast, mice depleted of only CD4 + T cells exhibited severe pulmonary inflammation and injury, decreased oxygenation and lung compliance, and increased respirations. Respiratory compromise was associated with the presence of activated CD8 + cells and neutrophils in broncho-alveolar lavage fluid. These observations provide direct experimental evidence that the host's response to P. carinii directly impairs pulmonary function and contributes to the pathogenesis of PCP. Furthermore, CD8 + T cells likely contribute to the respiratory compromise observed during PCP.
Pulmonary Inflammation Disrupts Surfactant Function during Pneumocystis carinii Pneumonia
Infection and Immunity, 2001
During Pneumocystis carinii pneumonia (PCP) in mice, the degree of pulmonary inflammation correlates directly with the severity of lung function deficits. Therefore, studies were undertaken to determine whether the host inflammatory response contributes to PCP-related respiratory impairment, at least in part, by disrupting the pulmonary surfactant system. Protein and phospholipid content and surfactant activity were measured in the lavage fluid of infected mice in either the absence or presence of an inflammatory response. At 9 weeks postinfection with P. carinii , nonreconstituted SCID mice exhibited no signs of pulmonary inflammation, respiratory impairment, or surfactant dysfunction. Lavage fluid obtained from these mice had protein/phospholipid (Pr/PL) ratios (64% ± 4.7%) and minimum surface tension values (4.0 ± 0.9 mN/m) similar to those of P. carinii -free control mice. However, when infected SCID mice were immunologically reconstituted, an intense inflammatory response ensue...