Bronchopneumonia with interstitial pneumonia in feedlot cattle: Epidemiologic characteristics of affected animals.

Bronchopneumonia with interstitial pneumonia (BIP) of feedlot cattle is characterized by gross and histologic lesions of cranioventral bronchopneumonia (BP) and caudodorsal interstitial pneumonia. This study described the characteristics and frequency of BIP in western Canadian feedlot cattle and identified epidemiologic differences between BIP and either BP or acute interstitial pneumonia (AIP). The study of 9909 deaths on 4 western Canadian feedlots included 1105 BIP, 1729 BP, and 878 AIP cases. A population of 55 cases with gross, histopathology, and microbiology data was used to validate the primary data set. BIP was the second most common reason for death (or euthanasia) from respiratory disease (1105/9909 cases), and the observed frequency was twice what was expected from random concurrence of BP and AIP. Based on logistic regression models, epidemiologic characteristics of BIP were comparable to those of BP, although BIP cases were more chronic with more instances of clinical illness prior to death. BIP was epidemiologically distinct from AIP. Specifically, BIP more frequently affected steers than heifers, deaths occurred earlier in the feeding period at lower body weights and lower daily weight gains, and BIP cases had longer durations from the first clinical illness to death and more separate instances of clinical illness prior to death. Furthermore, death from BIP mainly occurred in winter and fall, while death from AIP was most frequent in summer. These findings define BIP as a unique condition of feedlot cattle and suggest that chronic BP may promote the development of fatal interstitial lung disease in at-risk cattle.

Bronchopneumonia with interstitial pneumonia in beef feedlot cattle: Characterization and laboratory investigation.

Bronchopneumonia with interstitial pneumonia (BIP) has been considered a variant of acute interstitial pneumonia (AIP) rather than a distinct disease. This study compared 18 BIP, 24 bronchopneumonia (BP), and 13 AIP cases in feedlot beef cattle. Grossly, BIP cases typically had cranioventral lung lesions of similar morphology and extent as BP cases, but the caudodorsal lung appeared overinflated, bulged on section, and had interlobular edema and emphysema. Gross diagnosis of BIP had 83% sensitivity and 73% specificity relative to histopathology. Histologic lesions of BIP in cranioventral areas were of chronic BP, while caudodorsal lesions included alveolar and bronchiolar damage and inflammation, interstitial hypercellularity, and multifocal hemorrhages. In BIP cases, cranioventral lung lesions were more chronic than caudodorsal lesions. Histologic scores and microbiology data were comparable in cranioventral lung of BIP versus BP cases and caudodorsal lung of BIP versus AIP cases, with differences reflecting a more chronic disease involving less virulent bacteria in BIP versus BP. Mycoplasma bovis infection was similarly frequent among groups, and a viral cause of BIP was not identified. Lesion morphology and similar blood cytokine concentrations among groups argued against sepsis as a cause of lung injury. Surfactant dysfunction was identified in BIP and BP, and was only partially the result of protein exudation. These and other findings establish BIP as a distinct condition in which chronic cranioventral BP precedes acute caudodorsal interstitial lung disease, supporting a role of chronic inflammation in heightened sensitivity to 3-methylindole or another lung toxicant.

Mannheimia haemolytica serovars associated with respiratory disease in cattle in Great Britain.

BACKGROUND: Mannheimia haemolytica is commonly associated with respiratory disease in cattle worldwide as a cause of fibrinous pneumonia, bronchopneumonia and pleuritis. M. haemolytica is further subdivided into 12 serovars, however not all are considered to be pathogenic in cattle. The study aim was to determine the most common serovars of M. haemolytica associated with respiratory disease in cattle in Great Britain, which is currently unknown and could be useful information for clinicians when considering preventative strategies. RESULTS: One hundred four M. haemolytica isolates isolated from bovine clinical pathology and post-mortem samples from pneumonia cases between 2016 and 2018 were tested using a multiplex PCR assay to identify M. haemolytica serovars A1, A2 and A6. 46 isolates (44.2%) typed as M. haemolytica serovar A1, 31 (29.8%) as M. haemolytica serovar A2 and 18 isolates (17.3%) as M. haemolytica serovar A6. Nine isolates (8.7%) were not A1, A2 or A6 so were considered to belong to other serovars or were not typable. CONCLUSION: This study highlights the importance of M. haemolytica serovars other than A1 which may be responsible for respiratory disease in cattle and could help guide the veterinarian when making choices on preventative vaccination programmes.

Laboratory investigation of cases of fatal bacterial pneumonia in dairy cows.

Objective: Bacterial bronchopneumonia occurs in mature dairy cows but much of the information is extrapolated from knowledge of the disease in calves. The study was prompted by perceptions of an increasing occurrence and a paucity of information on fatal Mannheimia haemolytica pneumonia in dairy cows in Ontario. The study objectives were to describe the seasonality, main pathogens involved, and suggested predisposing factors for cases of fatal bacterial bronchopneumonia in mature dairy cows submitted for postmortem examination to a diagnostic laboratory, and to evaluate if the frequency of such submissions has increased over time. Animals: Mature dairy cows. Procedure: Retrospective study of cases submitted for postmortem examination to a diagnostic laboratory from 2007-2020 that were diagnosed as bacterial bronchopneumonia. Results: Most of the postmortem cases of bacterial bronchopneumonia in dairy cows were submitted from November to February (54% of cases). Mannheimia haemolytica was isolated from lung of 61/101 cases. Viruses were only identified in 8/55 cases tested. A minority (29/92) of bacterial isolates had in vitro resistance to antimicrobials used to treat pneumonia. Frequently suggested predisposing factors included recent introductions or movement of animals, recent or imminent calving, inclement weather, concurrent diseases, and poor ventilation in barns. Conclusion and clinical relevance: This study describes seasonal and annual trends, major pathogens, antimicrobial resistance profiles, and suggested predisposing factors in Ontario dairy cows submitted to a diagnostic laboratory for postmortem investigation of pneumonia and provides insights for understanding why outbreaks occur.

Objectif: La bronchopneumonie bactérienne survient chez les vaches laitières matures, mais une grande partie de l'information est extrapolée à partir de la connaissance de la maladie chez les veaux. L'étude a été motivée par la perception d'une occurrence croissante et d'un manque d'information sur la pneumonie mortelle à Mannheimia haemolytica chez les vaches laitières en Ontario. Les objectifs de l'étude étaient de décrire la saisonnalité, les principaux agents pathogènes impliqués et les facteurs prédisposants suggérés pour les cas de bronchopneumonie bactérienne mortelle chez les vaches laitières matures soumises à un examen post-mortem à un laboratoire de diagnostic, et d'évaluer si la fréquence de telles soumissions a augmenté au fil du temps. Animaux: Vaches laitières matures. Procédure: Étude rétrospective des cas soumis pour examen post-mortem à un laboratoire de diagnostic, entre 2007 et 2020, qui ont été diagnostiqués comme une bronchopneumonie bactérienne. Résultats: La plupart des cas post-mortem de bronchopneumonie bactérienne chez les vaches laitières ont été soumis de novembre à février (54 % des cas). Mannheimia haemolytica a été isolée du poumon de 61/101 cas. Des virus n'ont été identifiés que dans 8/55 cas testés. Une minorité (29/92) d'isolats bactériens présentaient une résistance in vitro aux antimicrobiens utilisés pour traiter la pneumonie. Les facteurs prédisposants fréquemment suggérés comprenaient des introductions ou des déplacements récents d'animaux, un vêlage récent ou imminent, des conditions météorologiques défavorables, des maladies concomitantes et une mauvaise ventilation dans les étables. Conclusion et pertinence clinique: Cette étude décrit les tendances saisonnières et annuelles, les principaux agents pathogènes, les profils de résistance aux antimicrobiens et les facteurs prédisposants suggérés chez les vaches laitières de l'Ontario soumises à un laboratoire de diagnostic pour une enquête post-mortem sur la pneumonie et fournit des informations pour comprendre pourquoi les épidémies se produisent.(Traduit par Dr Serge Messier).

Activation of Heme Oxygenase Expression by Cobalt Protoporphyrin Treatment Prevents Pneumonic Plague Caused by Inhalation of Yersinia pestis.

Pneumonic plague, caused by the Gram-negative bacteria Yersinia pestis, is an invasive, rapidly progressing disease with poor survival rates. Following inhalation of Y. pestis, bacterial invasion of the lungs and a tissue-damaging inflammatory response allows vascular spread of the infection. Consequently, primary pneumonic plague is a multiorgan disease involving sepsis and necrosis of immune tissues and the liver, as well as bronchopneumonia and rampant bacterial growth. Given the likely role of the hyperinflammatory response in accelerating the destruction of tissue, in this work we evaluated the therapeutic potential of the inducible cytoprotective enzyme heme oxygenase 1 (HO-1) against primary pneumonic plague. On its own, the HO-1 inducer cobalt protoporphyrin IX (CoPP) provided mice protection from lethal challenge with Y. pestis CO92 with improved pulmonary bacterial clearance and a dampened inflammatory response compared to vehicle-treated mice. Furthermore, CoPP treatment combined with doxycycline strongly enhanced protection in a rat aerosol challenge model. Compared to doxycycline alone, CoPP treatment increased survival, with a 3-log decrease in median bacterial titer recovered from the lungs and the general absence of a systemic hyperinflammatory response. In contrast, treatment with the HO-1 inhibitor SnPP had no detectable impact on doxycycline efficacy. The combined data indicate that countering inflammatory toxicity by therapeutically inducing HO-1 is effective in reducing the rampant growth of Y. pestis and preventing pneumonic plague.

Regeneration of Pulmonary Tissue in a Calf Model of Fibrinonecrotic Bronchopneumonia Induced by Experimental Infection with Chlamydia Psittaci.

Pneumonia is a cause of high morbidity and mortality in humans. Animal models are indispensable to investigate the complex cellular interactions during lung injury and repair in vivo. The time sequence of lesion development and regeneration is described after endobronchial inoculation of calves with Chlamydia psittaci. Calves were necropsied 2-37 days after inoculation (dpi). Lesions and presence of Chlamydia psittaci were investigated using histology and immunohistochemistry. Calves developed bronchopneumonia at the sites of inoculation. Initially, Chlamydia psittaci replicated in type 1 alveolar epithelial cells followed by an influx of neutrophils, vascular leakage, fibrinous exudation, thrombosis and lobular pulmonary necrosis. Lesions were most extensive at 4 dpi. Beginning at 7 dpi, the number of chlamydial inclusions declined and proliferation of cuboidal alveolar epithelial cells and sprouting of capillaries were seen at the periphery of necrotic tissue. At 14 dpi, most of the necrosis had been replaced with alveoli lined with cuboidal epithelial cells resembling type 2 alveolar epithelial cells and mild fibrosis, and hyperplasia of organized lymphoid tissue were observed. At 37 dpi, regeneration of pulmonary tissue was nearly complete and only small foci of remodeling remained. The well-defined time course of development and regeneration of necrotizing pneumonia allows correlation of morphological findings with clinical data or treatment regimen.

ASPIRATION BRONCHOPNEUMONIA BY ACINETOBACTER BAUMANNII IN A WILDLIFE EUROPEAN HARE (LEPUS EUROPAEUS) IN BRAZIL.

Acinetobacter baumannii is a major cause of illness in hospitalized patients and the most important and common pathogen in nosocomial outbreaks worldwide. In animals, A. baumannii has been associated with respiratory infections in a group of minks, leading to pneumonia and acute mortality. This report documents a case of aspiration bronchopneumonia in a wild European hare caused by A. baumannii. A free-ranging, adult male European hare was submitted to necropsy after acute trauma due to being hit by a car. Its lungs showed consolidation with abscess in the middle and cranial lobes. Histopathologic evaluation revealed liquefactive necrosis associated with neutrophilic infiltration, cellular debris, plant material, and bacterial myriads surrounded by moderate neutrophils, macrophages, multinucleated giant cells, lymphocytes, and plasma cell inflammation. Acinetobacter baumannii was isolated from lung tissue.

Development of Bacterial Therapeutics against the Bovine Respiratory Pathogen Mannheimia haemolytica.

Bovine respiratory disease (BRD) is a major cause of morbidity and mortality in beef cattle. Recent evidence suggests that commensal bacteria of the bovine nasopharynx have an important role in maintaining respiratory health by providing colonization resistance against pathogens. The objective of this study was to screen and select bacterial therapeutic candidates from the nasopharynxes of feedlot cattle to mitigate the BRD pathogen Mannheimia haemolytica In a stepwise approach, bacteria (n = 300) isolated from the nasopharynxes of 100 healthy feedlot cattle were identified and initially screened (n = 178 isolates from 12 different genera) for growth inhibition of M. haemolytica Subsequently, selected isolates were evaluated for the ability to adhere to bovine turbinate (BT) cells (n = 47), compete against M. haemolytica for BT cell adherence (n = 15), and modulate gene expression in BT cells (n = 10). Lactobacillus strains had the strongest inhibition of M. haemolytica, with 88% of the isolates (n =33) having inhibition zones ranging from 17 to 23 mm. Adherence to BT cells ranged from 3.4 to 8.0 log10 CFU per 105 BT cells. All the isolates tested in competition assays reduced M. haemolytica adherence to BT cells (32% to 78%). Among 84 bovine genes evaluated, selected isolates upregulated expression of interleukin 8 (IL-8) and IL-6 (P < 0.05). After ranking isolates for greatest inhibition, adhesion, competition, and immunomodulation properties, 6 Lactobacillus strains from 4 different species were selected as the best candidates for further development as intranasal bacterial therapeutics to mitigate M. haemolytica infection in feedlot cattle.IMPORTANCE Bovine respiratory disease (BRD) is a significant animal health issue impacting the beef industry. Current BRD prevention strategies rely mainly on metaphylactic use of antimicrobials when cattle enter feedlots. However, a recent increase in BRD-associated bacterial pathogens that are resistant to metaphylactic antimicrobials highlights a pressing need for the development of novel mitigation strategies. Based upon previous research showing the importance of respiratory commensal bacteria in protecting against bronchopneumonia, this study aimed to develop bacterial therapeutics that could be used to mitigate the BRD pathogen Mannheimia haemolytica Bacteria isolated from the respiratory tracts of healthy cattle were characterized for their inhibitory, adhesive, and immunomodulatory properties. In total, 6 strains were identified as having the best properties for use as intranasal therapeutics to inhibit M. haemolytica If successful in vivo, these strains offer an alternative to metaphylactic antimicrobial use in feedlot cattle for mitigating BRD.

Pathogenic variability among Pasteurella multocida type A isolates from Brazilian pig farms.

BACKGROUND: Pasteurella multocida type A (PmA) is considered a secondary agent of pneumonia in pigs. The role of PmA as a primary pathogen was investigated by challenging pigs with eight field strains isolated from pneumonia and serositis in six Brazilian states. Eight groups of eight pigs each were intranasally inoculated with different strains of PmA (1.5 mL/nostril of 10e7 CFU/mL). The control group (n = 12) received sterile PBS. The pigs were euthanized by electrocution and necropsied by 5 dpi. Macroscopic lesions were recorded, and swabs and fragments of thoracic and abdominal organs were analyzed by bacteriological and pathological assays. The PmA strains were analyzed for four virulence genes (toxA: toxin; pfhA: adhesion; tbpA and hgbB: iron acquisition) by PCR and sequencing and submitted to multilocus sequence typing (MLST). RESULTS: The eight PmA strains were classified as follows: five as highly pathogenic (HP) for causing necrotic bronchopneumonia and diffuse fibrinous pleuritis and pericarditis; one as low pathogenic for causing only focal bronchopneumonia; and two as nonpathogenic because they did not cause injury to any pig. PCR for the gene pfhA was positive for all five HP isolates. Sequencing demonstrated that the pfhA region of the HP strains comprised four genes: tpsB1, pfhA1, tpsB2 and pfhA2. The low and nonpathogenic strains did not contain the genes tpsB2 and pfhA2. A deletion of four bases was observed in the pfhA gene in the low pathogenic strain, and an insertion of 37 kb of phage DNA was observed in the nonpathogenic strains. MLST clustered the HP isolates in one group and the low and nonpathogenic isolates in another. Only the nonpathogenic isolates matched sequence type 10; the other isolates did not match any type available in the MLST database. CONCLUSIONS: The hypothesis that some PmA strains are primary pathogens and cause disease in pigs without any co-factor was confirmed. The pfhA region, comprising the genes tpsB1, tpsB2, pfhA1 and pfhA2, is related to the pathogenicity of PmA. The HP strains can cause necrotic bronchopneumonia, fibrinous pleuritis and pericarditis in pigs and can be identified by PCR amplification of the gene pfhA2.

In vivo efficacy and pharmacokinetics of bi-aryl oxazolidinone RBx 11760 loaded polylactic acid-polyethylene glycol nanoparticles in mouse hematogenous bronchopneumonia and rat groin abscess caused by Staphylococcus aureus.

RBx 11760 is a bi-aryl oxazolidinone antibacterial agent active against Staphylococcus aureus but has poor solubility. Here we have encapsulated RBx 11760 in PLA-PEG NPs with an aim to improve physicochemical, pharmacokinetics and in vivo efficacy. The average size and zeta potential of RBx 11760 loaded NPs were found to be 106.4 nm and -22.2 mV, respectively. The absolute size of nanoparticles by HRTEM was found to be approximately 80 nm. In vitro antibacterial agar well diffusion assay showed clear zone of inhibition of bacterial growth. In pharmacokinetic study, nanoparticle showed 4.6-fold and 7-fold increase in AUCinf and half-life, respectively, as compared to free drug. RBx 11760 nanoparticle significantly reduced bacterial counts in lungs and improved the survival rate of immunocompromised mice as compared to free drugs. Thus, RBx 11760 loaded nanoparticles have strong potential to be used as nanomedicine against sensitive and drug resistant Staphylococcus aureus infections.

Fatal fibrino-hemorrhagic bronchopneumonia associated with Morganella morganii in a bottlenose dolphin: a case report.

A 5 yr old, 184 kg, and 262 cm total length female bottlenose dolphin Tursiops truncatus was found dead in a display after bloody discharge from the blowhole was observed 3 h prior to death. Pathological examination revealed fibrinous bronchopneumonia with prominent areas of necrosis (sequestra) and numerous Gram-negative bacilli within alveoli and in blood vessels of the lungs and liver and between muscle fibers. The cause of death was attributed to septicemia. Often, cases of fibrinous bronchopneumonia are characterized by bacteremia in the latter stages of infection, resulting in the death of the animal. Septicemia likely accounts for the ecchymoses and petechiae noted on the spleen, pancreas, forestomach, lungs, visceral peritoneum, and small intestine. Additional lesions included hemothorax, stable red frothy fluid in the trachea, and lymphoid depletion in the spleen and lymph nodes. Pure growth of Morganella morganii was isolated from the lungs, blood, liver, and blowhole mucosa. Sequencing of 16s rRNA of the isolated bacteria showed more than 99.6% identity with M. morganii strain FDAARGOS_172. To our knowledge, this is the first report of fatal fibrinonecrotizing bronchopneumonia associated with M. morganii infection in a cetacean.

Ex Vivo Perfusion Treatment of Infection in Human Donor Lungs.

Ex vivo lung perfusion (EVLP) is a platform to treat infected donor lungs with antibiotic therapy before lung transplantation. Human donor lungs that were rejected for transplantation because of clinical concern regarding infection were randomly assigned to two groups. In the antibiotic group (n = 8), lungs underwent EVLP for 12 h with high-dose antibiotics (ciprofloxacin 400 mg or azithromycin 500 mg, vancomycin 15 mg/kg, and meropenem 2 g). In the control group (n = 7), lungs underwent EVLP for 12 h without antibiotics. A quantitative decrease in bacterial counts in bronchoalveolar lavage (BAL) was found in all antibiotic-treated cases but in only two control cases. Perfusate endotoxin levels at 12 h were significantly lower in the antibiotic group compared with the control group. EVLP with broad-spectrum antibiotic therapy significantly improved pulmonary oxygenation and compliance and reduced pulmonary vascular resistance. Perfusate endotoxin levels at 12 h were strongly correlated with levels of perfusates tumor necrosis factor α, IL-1ß and macrophage inflammatory proteins 1α and 1ß at 12 h. In conclusion, EVLP treatment of infected donor lungs with broad-spectrum antibiotics significantly reduced BAL bacterial counts and endotoxin levels and improved donor lung function.

Rare cause of natural death in forensic setting: hemophagocytic syndrome.

We report about the case of a sudden unexpected death of a 25-year-old male suffering from infectious disease. An autopsy was ordered with no final premortem diagnosis. Microscopic and microbiological examination revealed a pneumococcal bronchopneumonia and hemophagocytic lesions in the bone marrow. After integrating clinical and autopsy reports as well as additional postmortem investigations, the cause of death was found to be infectious-triggered hemophagocytic syndrome (HPS) with a final cytokine storm. This seems to be the first reported fatal case of a reactive form of HPS associated to Streptococcus pneumoniae to the best of our knowledge. HPS is a dangerous hyperinflammation with highly characteristic, but nonspecific, laboratory findings and symptoms. Autopsies in such cases must be carefully performed and include systematic tissue sampling done by an experienced pathologist.

Amphisomal route of MHC class I cross-presentation in bacteria-infected dendritic cells.

Dendritic cells (DCs) are among the first professional APCs encountered by the obligate intracellular bacterium Chlamydia during infection. Using an established mouse bone marrow-derived DC line, we show that DCs control chlamydial infection in multiple small inclusions characterized by restricted bacterial growth, impaired cytosolic export of the virulence factor chlamydial protease-like activity factor, and interaction with guanylate-binding protein 1, a host cell factor involved in the initiation of autophagy. During maturation of infected DCs, chlamydial inclusions disintegrate, likely because they lack chlamydial protease-like activity factor-mediated protection. Released cytosolic Chlamydia are taken up by autophagosomes and colocalize with cathepsin-positive amphisomal vacuoles, to which peptide transporter TAP and upregulated MHC class I (MHC I) are recruited. Chlamydial Ags are subsequently generated through routes involving preprocessing in amphisomes via cathepsins and entry into the cytosol for further processing by the proteasome. Finally, bacterial peptides are reimported into the endosomal pathway for loading onto recycling MHC I. Thus, we unravel a novel pathway of MHC I-mediated cross-presentation that is initiated with a host cellular attack physically disrupting the parasitophorous vacuole, involves autophagy to collect cytosolic organisms into autophagosomes, and concludes with complex multistep antigenic processing in separate cellular compartments.

Glutaredoxin-1 attenuates S-glutathionylation of the death receptor fas and decreases resolution of Pseudomonas aeruginosa pneumonia.

RATIONALE: The death receptor Fas is critical for bacterial clearance and survival of mice after Pseudomonas aeruginosa infection. OBJECTIVES: Fas ligand (FasL)-induced apoptosis is augmented by S-glutathionylation of Fas (Fas-SSG), which can be reversed by glutaredoxin-1 (Grx1). Therefore, the objective of this study was to investigate the interplay between Grx1 and Fas in regulating the clearance of P. aeruginosa infection. METHODS: Lung samples from patients with bronchopneumonia were analyzed by immunofluorescence. Primary tracheal epithelial cells, mice lacking the gene for Grx1 (Glrx1(-/-)), Glrx1(-/-) mice treated with caspase inhibitor, or transgenic mice overexpressing Grx1 in the airway epithelium were analyzed after infection with P. aeruginosa. MEASUREMENTS AND MAIN RESULTS: Patient lung samples positive for P. aeruginosa infection demonstrated increased Fas-SSG compared with normal lung samples. Compared with wild-type primary lung epithelial cells, infection of Glrx1(-/-) cells with P. aeruginosa showed enhanced caspase 8 and 3 activities and cell death in association with increases in Fas-SSG. Infection of Glrx1(-/-) mice with P. aeruginosa resulted in enhanced caspase activity and increased Fas-SSG as compared with wild-type littermates. Absence of Glrx1 significantly enhanced bacterial clearance, and decreased mortality postinfection with P. aeruginosa. Inhibition of caspases significantly decreased bacterial clearance postinfection with P. aeruginosa, in association with decreased Fas-SSG. In contrast, transgenic mice that overexpress Grx1 in lung epithelial cells had significantly higher lung bacterial loads, enhanced mortality, decreased caspase activation, and Fas-SSG in the lung after infection with P. aeruginosa, compared with wild-type control animals. CONCLUSIONS: These results suggest that S-glutathionylation of Fas within the lung epithelium enhances epithelial apoptosis and promotes clearance of P. aeruginosa and that glutaredoxin-1 impairs bacterial clearance and increases the severity of pneumonia in association with deglutathionylation of Fas.

Dysregulation of claudin-5 in HIV-induced interstitial pneumonitis and lung vascular injury. Protective role of peroxisome proliferator-activated receptor-γ.

RATIONALE: HIV-1-induced interstitial pneumonitis (IP) is a serious complication of HIV-1 infection, characterized by inflammation and cellular infiltration in lungs, often leading to respiratory failure and death. The barrier function of the pulmonary endothelium is caused in part by tight junction (TJ) proteins, such as claudin-5. Peroxisome proliferator-activated receptor (PPAR)-γ is expressed in lung tissues and regulates inflammation. We hypothesize that HIV-1 induces vascular lung injury, and HIV-1-mediated damage of the pulmonary endothelium and IP is associated with dysregulation of PPAR-γ. OBJECTIVES: Investigate the effects of HIV-1 infection on the pulmonary microvasculature and the modulatory effects of the PPAR-γ ligands. METHODS: Using human lung tissues, we demonstrated down-regulation of claudin-5 (marker of pulmonary barrier integrity), down-regulation of PPAR-γ transcription, and expression in lung tissues of HIV-1-infected humans with IP. MEASUREMENTS AND MAIN RESULTS: Human lung microvascular endothelial cells expressed the TJ proteins claudin-5, ZO-1, and ZO-2; HIV-1 decreased TJ proteins expression and induced nuclear factor-κB promoter activity, which was reversed by PPAR-γ agonist. Using two murine HIV/AIDS models, we demonstrated decreased claudin-5 expression and increased macrophage infiltration in the lungs of HIV-1-infected animals. Activation of PPAR-γ prevented HIV-1-induced claudin-5 down-regulation and significantly reduced viremia and pulmonary macrophage infiltration. CONCLUSIONS: HIV-induced IP is associated with injury to the lung vascular endothelium, with decreased TJ and PPAR-γ expression, and increased pulmonary macrophage infiltration. PPAR-γ ligands abrogated these effects. Thus, regulation of PPAR-γ can be a therapeutic approach against HIV-1-induced vascular damage and IP in infected humans. Removal of Expression of Concern: Issues leading to the previous expression of concern for this article have been resolved after further revisions and editorial review. No further concerns exist.

Development and characterization of a long-term murine model of Streptococcus pneumoniae infection of the lower airways.

Chronic obstructive pulmonary disease (COPD) is characterized by long periods of stable symptoms, but exacerbations occur, which result in a permanent worsening of symptoms. Previous studies have shown a link between bacterial colonization of the lower airways of COPD sufferers and an increase in exacerbation frequency. One of the most frequent bacterial colonizers is Streptococcus pneumoniae. To mimic this aspect of COPD, a murine model of low-level pneumococcal colonization in the lung has been developed, in which S. pneumoniae persisted in the lungs for at least 28 days. From day 14 postinfection, bacterial numbers remained constant until at least 28 days postinfection, and animals showed no outward signs of disease. The bacterial presence correlated with a low-level inflammatory response that was localized to small foci across the left and inferior lobes of the lung. The cellular response was predominantly monocytic, and focal fibroplasia was observed at the airway transitional zones. Physiological changes in the lungs were investigated with a Forced Maneuvers system. This new model provides a means of study of a long-term pulmonary infection with a human pathogen in a rodent system. This is an excellent tool for the development of future models that mimic complex respiratory diseases such as COPD and asthma.

Chest computed tomography for the diagnosis of Mycoplasma pneumoniae infection.

We analysed 53 cases of laboratory-confirmed Mycoplasma pneumoniae infection with cough lasting ≥ 7 days and chest radiography showing no abnormal findings. Twenty-two (41%) of those patients showed abnormal findings on chest high-resolution computed tomography. In the daily clinical setting, for assessment of acute cough, physicians should be aware that it is difficult to confirm bronchiolitis or bronchopneumonia due to M. pneumoniae by chest radiography.

Pathology of experimental infection by Pasteurella multocida serotype A: 1 in buffalo calves.

Pasteurella multocida serotype A:3 has been mostly implicated in pneumonic pasteurellosis in ruminants. In contrast, our previous studies have reported that both serotypes A:1 and A:3 were responsible for respiratory diseases in cattle and buffaloes. However, the pathology and pathogenesis of P. multocida serotype A:1 (Pm A:1) infection have not been studied in ruminants. In the present study, 12- to 15-week-old buffalo calves (Bubalus bubalis) infected by Pm A:1 had fibrinous and suppurative bronchopneumonia with focal areas of coagulation necrosis typical of pneumonic pasteurellosis. For the first time, this study reports the lung pathology and pathogenecity of Pm A:1 infection in calves.

Equine pulmonary aspergillosis with encephalitic, myocardial, and renal dissemination.

The cause of the death of a 16-month-old Brasileiro-de-Hipismo filly and a 3-year-old male Paint Horse with clinical manifestations of anemia and apathy from southern Brazil was investigated. These horses were maintained at the same stable; received hay as part of their diet and were submitted for routine necropsy evaluations. Significant gross findings included several nodules randomly distributed throughout the pulmonary lobes of both horses, and the kidneys, myocardium, and the frontal lobes of the cerebrum of the filly. Histopathological evaluation revealed pyogranulomatous bronchopneumonia in both horses; granulomatous interstitial nephritis, myocarditis, and encephalitis were observed in the filly. All lesions contained vasculitis and thrombosis associated with myriads of intralesional, branching, septate fungi consistent with Aspergillus spp.; intralesional fungi were more easily identified by the Grocott methenamine silver stain. Mycological culture of fresh pulmonary sections from both horses and the brain of the filly revealed pure growths of A. fumigatus. These findings confirmed the participation of A. fumigatus in the etiopathogenesis of the lesions observed in the lungs of both horses, and the cerebrum, myocardium and kidneys of the filly and might represent the first description of A. fumigatus-induced encephalitis in horses. Additionally, we believe that infection occurred during the ingestion of contaminated hay or by inhalation of spores within contaminated bedding that resulted in transient nasal mycosis, which progressed to pyogranulomatous bronchopneumonia in both horses with embolic encephalitic, myocardial, and renal dissemination of A. fumigatus occurring only in the filly.