Opportunistic Lung Infections Research Articles

Supporting Patients with Nontuberculous Mycobacterial Pulmonary Disease: Ensuring Best Practice in UK Healthcare Settings.

Nontuberculous mycobacterial pulmonary disease (NTM-PD) results from opportunistic lung infections by mycobacteria other than Mycobacterium tuberculosis or Mycobacterium leprae species. Similar to many other countries, the incidence of NTM-PD in the United Kingdom (UK) is on the rise for reasons that are yet to be determined. Despite guidelines established by the American Thoracic Society (ATS), the Infectious Diseases Society of America, and the British Thoracic Society, NTM-PD diagnosis and management remain a significant clinical challenge. In this review article, we comprehensively discuss key challenges in NTM-PD diagnosis and management, focusing on the UK healthcare setting. We also propose countermeasures to overcome these challenges and improve the detection and treatment of patients with NTM-PD.

Pneumocystis jiroveci Pneumonia secondary to tyrosine kinase inhibitor with blinatumomab therapy: A case report.

Pneumocystis jiroveci Pneumonia (PCP) is a common cause of opportunistic lung infection and is associated with high mortality in immunocompromised patients. Few reports describe pneumocystis jiroveci as a causative agent of tyrosine kinase inhibitor or blinatumomab related infections. Case presentation A 64-year-old man with philadelphia chromosome positive acute lymphoblastic leukemia (ALL) presented to the intensive care unit with intermittent high fever and shortness of breath. Three cycles of tyrosine kinase inhibitor (TKI) with blinatumomab therapy were given in recent 4months. Next-generation sequencing of bronchoalveolar lavage fluid and peripheral blood showed pneumocystis jiroveci. After trimethoprim- sulfamethoxazole treatment and subsequent mechanical ventilation, the infection was controlled successfully. Due to susceptibility and early onset of PCP in ALL patients received TKI combined with blinatumomab therapy, so we should be alert to PCP when pulmonary infection occurred.

Efficacy of sulfasalazine for the prevention of Pneumocystis pneumonia in patients with rheumatoid arthritis: A multicentric self-controlled case series study

IntroductionPneumocystis pneumonia (PCP) is an opportunistic lung infection and has been reported among patients with rheumatoid arthritis (RA). An animal study revealed that sulfasalazine enhances Pneumocystis clearance from the lung by accelerating macrophage activity. MethodsThe self-controlled case series (SCCS) method was used to investigate the association between sulfasalazine use and PCP development in patients with RA without the effect of time-invariant, interpatient confounders. PCP episodes which developed in patients with RA at five hospitals between 2003 and 2019 were identified. PCP was defined by the following criteria: 1) detection of Pneumocystis jirovecii in respiratory specimens by polymerase chain reaction; 2) clinical symptoms (pyrexia, dry cough, dyspnea or hypoxia); 3) diffuse interstitial infiltrate on chest imaging; and 4) absence of PCP prophylaxis. The PCP incidence rate ratio (IRR) was compared between periods with and without sulfasalazine use by conditional Poisson regression. ResultsFifty episodes of PCP were identified in 49 patients. Thirty patients received sulfasalazine at some point during their observation. While 49 episodes of PCP developed in 170.3 person-years without sulfasalazine use, only one episode of PCP developed in 103.7 person-years with sulfasalazine use. Sulfasalazine use was associated with a decreased PCP risk (adjusted IRR <0.01; 95% confidence interval <0.01–0.03) after adjusting for age and glucocorticoid, methotrexate, and tumor necrosis factor inhibitor administration. ConclusionOur study demonstrated a preventive effect of sulfasalazine against PCP in patients with RA.

65-Year-Old Man With Weight Loss and Dyspnea on Exertion

65-Year-Old Man With Weight Loss and Dyspnea on Exertion

The effect of a new coronavirus infection (COVID-19) on clinical and radiological manifestations in patients with comorbidity of respiratory tuberculosis, HIV-infection and opportunistic lung diseases: prospective study design

Aim. To study the features of clinical and radiological manifestations and diagnosis of COVID-19, respiratory tuberculosis and opportunistic lung infections (OIL) coinfection in patients with late stages of HIV-infection with immunodeficiency.&#x0D; Materials and methods. The study included 29 patients with COVID-19 coinfection, respiratory tuberculosis and opportunistic lung infections in the late stages of HIV-infection with immunodeficiency (group 1) and 29 patients similar in all parameters without COVID-19 (group 2). All patients were underwent clinical and laboratory, radiation and bronchological examination, and microbiological, immunological, molecular genetic, cytological and histological examination of diagnostic material of the respiratory tract, cerebrospinal and pleural fluid, blood, urine and feces to identify pathogens of coinfection. Statistical data processing was carried out using the Microsoft Office Excel 2010 program with the calculation of the average in the group and the standard error of the average, confidence interval.&#x0D; Results. It has been established that co-infection with COVID-19, respiratory tuberculosis and opportunistic lung infections in patients with late stages of HIV-infection with immunodeficiency is manifested by a pronounced intoxication syndrome, bronchopulmonary manifestations and symptoms of damage to other organs and systems, which is due to the generalization of tuberculosis with extrapulmonary lesions and the development of opportunistic lung infections, as in patients without COVID-19. A computed tomogram of the chest organs with this coinfection visualizes the syndrome of dissemination, the syndrome of adenopathy and the syndrome of pathology of the pulmonary pattern, represented by the compaction of interstitial tissue in the frosted glass type, which is associated with the simultaneous layering of various pathologies, which complicates their differential diagnosis. This determines the similarity of clinical and radiological manifestations of COVID-19 coinfection, respiratory tuberculosis and opportunistic lung infections in patients with late-stage HIV-infection with immunodeficiency, as in patients without COVID-19. This requires complex microbiological and molecular genetic research methods to identify specific pathogens for the appointment of timely treatment.&#x0D; Conclusion. Patients with COVID-19 coinfection, respiratory tuberculosis and opportunistic lung infections in the late stages of HIV-infection with immunodeficiency pose a high risk of infection in a healthy population, taking into account their social maladaptation and non-adherence to examination and treatment. This requires an active diagnosis of COVID-19 in all patients with respiratory tuberculosis and HIV-infection who are registered in the office of anti-tuberculosis care for HIV-infected in an anti-tuberculosis dispensary, for emergency isolation and treatment.

Development of a Droplet Digital Polymerase Chain Reaction for Sensitive Detection of Pneumocystis jirovecii in Respiratory Tract Specimens.

Background: Pneumocystis jirovecii is a human-specific opportunistic fungus that causes Pneumocystis pneumonia (PCP), a life-threatening opportunistic lung infection that affects immunocompromised patients. P. jirovecii colonization may be linked to the transmission of the infection. The detection of P. jirovecii in immunocompromised patients is thus especially important. The low fungal load and the presence of PCR inhibitors limit the usefulness of quantitative PCR (qPCR) for accurate absolute quantification of P. jirovecii in specimens. Droplet digital PCR (ddPCR), however, presents a methodology that allows higher sensitivity and accuracy. Here, we developed a ddPCR method for detecting P. jirovecii DNA in respiratory specimens, and evaluated its sensitivity against qPCR.Materials and Methods: One bronchoalveolar fluid (BALF) sample each was collected from 82 patients with potential PCP to test the presence of P. jirovecii DNA using both ddPCR and qPCR, and samples with inconsistent results between the two methods were further tested by metagenomic next generation sequencing (mNGS). In addition, 37 sputum samples from 16 patients diagnosed with PCP, as well as continuous respiratory tract specimens from nine patients with PCP and treated with sulfonamides, were also collected for P. jirovecii DNA testing using both ddPCR and qPCR.Results: ddPCR and qPCR gave the same results for 95.12% (78/82) of the BALF samples. The remaining four specimens tested positive using ddPCR but negative using qPCR, and they were found to be positive by mNGS. Detection results of 78.37% (29/37) sputum samples were consistent between ddPCR and qPCR, while the other eight samples tested positive using ddPCR but negative using qPCR. The P. jirovecii load of patients with PCP decreased to undetectable levels after treatment according to qPCR, but P. jirovecii was still detectable using ddPCR.Conclusions: ddPCR was more sensitive than qPCR, especially at detecting low-pathogen-load P. jirovecii. Thus, ddPCR represents a useful, viable, and reliable alternative to qPCR in P. jirovecii testing in patients with immunodeficiency.

Burkholderia cenocepacia transcriptome during the early contacts with giant plasma membrane vesicles derived from live bronchial epithelial cells

Burkholderia cenocepacia is known for its capacity of adherence and interaction with the host, causing severe opportunistic lung infections in cystic fibrosis patients. In this work we produced Giant Plasma Membrane Vesicles (GPMVs) from a bronchial epithelial cell line and validated their use as a cell-like alternative to investigate the steps involved in the adhesion process of B. cenocepacia. RNA-sequencing was performed and the analysis of the B. cenocepacia K56-2 transcriptome after the first contacts with the surface of host cells allowed the recognition of genes implicated in bacterial adaptation and virulence-associated functions. The sensing of host membranes led to a transcriptional shift that caused a cascade of metabolic and physiological adaptations to the host specific environment. Many of the differentially expressed genes encode proteins related with central metabolic pathways, transport systems, cellular processes, and virulence traits. The understanding of the changes in gene expression that occur in the early steps of infection can uncover new proteins implicated in B. cenocepacia-host cell adhesion, against which new blocking agents could be designed to control the progression of the infectious process.

Hemoptysis in Renal Transplant Recipients.

Background:Hemoptysis is the expectoration of blood from respiratory system. Clinical entities associated with hemoptysis in renal transplant recipients differ from those causing hemoptysis in common population. This review summarizes all reported clinical conditions related to hemoptysis in renal transplant patients, their causes, diagnostic approach and management. Methods and Materials:Primary literature was researched through MEDLINE/PubMed database and Google Scholar without restrictions. Relevant and current literatures related to hemoptysis in renal transplant recipients were used. Results:Overall 23 articles were included, since they report clinical conditions associated with hemoptysis in renal transplant recipients. Opportunistic lung infections, pulmonary hemorrhage associated with drugs and malignancies are usual causes of hemoptysis in these patients, sometimes with a fatal outcome.Conclusions:Hemoptysis is an important manifestation in renal transplant patients, caused frequently by rare clinical entities, different from those in common population.

Особенности клинических проявлений и диагностики сочетания туберкулеза органов дыхания с оппортунистическими инфекциями легких у взрослых больных на поздних стадиях ВИЧ-инфекции с иммунодефицитом

Aim. To study the features of clinical manifestations and diagnostics of a combination of pulmonary tuberculosis (PTB) and opportunistic lung infections (OLI) in patients in advanced stage of HIV infection with immunodeficiency. Materials and methods. The study included 338 patients with newly diagnosed PTB with isolation of Mycobacterium tuberculosis, aged 25–60 years, having stage 4B and 5 HIV infection in a stage of progression, with no antiretroviral therapy, who were divided into 2 groups: 169 patients with a combination of PTB and OLI (main group) and 169 – with PTB (comparison group). All patients underwent clinical and laboratory, radiation and bronchological examination, as well as microbiological, immunological, molecular and genetic, cytological and histological examination of the diagnostic material from the respiratory tract, cere-brospinal and pleural fluid, blood, urine and feces in order to reveal OLI. Statistical analysis was carried out using Microsoft Office Excel 2010, data are presented as mean and standard deviation, the confidence interval. Results. It was found that tuberculosis in patients of the main group and the comparison group was generalized with multiple lesions and extrapulmonary phe-nomena, which include severe intoxication syndrome, bronchopulmonary lesions and symptoms of other organs and systems disorders. These made it difficult to differentiate between the PTB+OLI combination and PTB, and their diagnosis is possible only when M. tuberculosis and causative agents of other OLI are de-tected. If there is a combination of several lung diseases, chest computed tomography shows dissemination syndrome, adenopathy syndrome and lung pattern pathology syndrome, which looks like ground-glass opacity. In these cases, the PTB+OLI combination played not the least role, which together with direct lung lesions by HIV, made it impossible to differentiate these pathologies. The difference was possible only when M. tuberculosis and causative agents of other OLI were identified. Conclusion. With study data, an algorithm for the sequential etiological diagnosis of the PTB and OLI combination in patients with advanced stages of HIV infection with immunodeficiency was proposed.

TGF-\u03b21 increases viral burden and promotes HIV-1 latency in primary differentiated human bronchial epithelial cells

Combination antiretroviral therapy (cART) has increased the life expectancy of HIV patients. However, the incidence of non-AIDS associated lung comorbidities, such as COPD and asthma, and that of opportunistic lung infections have become more common among this population. HIV proteins secreted by the anatomical HIV reservoirs can have both autocrine and paracrine effects contributing to the HIV-associated comorbidities. HIV has been recovered from cell-free bronchoalveolar lavage fluid, alveolar macrophages, and intrapulmonary lymphocytes. We have recently shown that ex-vivo cultured primary bronchial epithelial cells and the bronchial brushings from human subjects express canonical HIV receptors CD4, CCR5 and CXCR4 and can be infected with HIV. Together these studies suggest that the lung tissue can serve as an important reservoir for HIV. In this report, we show that TGF-β1 promotes HIV latency by upregulating a transcriptional repressor BLIMP-1. Furthermore, we identify miR-9-5p as an important intermediate in TGF-β-mediated BLIMP-1 upregulation and consequent HIV latency. The transcriptionally suppressed HIV can be reactivated by common latency reactivating agents. Together our data suggest that in patients with chronic airway diseases, TGF-β can elevate the HIV viral reservoir load that could further exacerbate the HIV associated lung comorbidities.

Antifungal Phenylpropanoid Glycosides from Lippia rubella.

Lippia species share various pharmacological activities and are used in traditional cooking and medicine worldwide. Combined chromatographic techniques such as column chromatography, high-performance liquid chromatography, and countercurrent chromatography led to the purification of two new antifungal phenylpropanoid glycosides, lippiarubelloside A (1) and lippiarubelloside B (2), by bioactivity-directed fractionation of an ethanol-soluble extract from Lippia rubella, in addition to the known active related compounds forsythoside A (3), verbascoside (4), isoverbascoside (5), and poliumoside (6). The structures of compounds 1 and 2 were determined by comparison of their NMR spectroscopic data with the prototype active compound 4. Cryptococcus neoformans, which causes opportunistic lung infections, was sensitive to compounds 1-6 in the concentration range of 15-125 μg/mL. A synergistic effect (FICindex = 0.5) between 3 and amphotericin B was demonstrated. The glycosylated flavonoids pectolinarin (7), linarin (8), and siparunoside (9) were also isolated.

Linocin and OmpW Are Involved in Attachment of the Cystic Fibrosis-Associated Pathogen Burkholderia cepacia Complex to Lung Epithelial Cells and Protect Mice against Infection.

Members of the Burkholderia cepacia complex (Bcc) cause chronic opportunistic lung infections in people with cystic fibrosis (CF), resulting in a gradual lung function decline and, ultimately, patient death. The Bcc is a complex of 20 species and is rarely eradicated once a patient is colonized; therefore, vaccination may represent a better therapeutic option. We developed a new proteomics approach to identify bacterial proteins that are involved in the attachment of Bcc bacteria to lung epithelial cells. Fourteen proteins were reproducibly identified by two-dimensional gel electrophoresis from four Bcc strains representative of two Bcc species: Burkholderia cenocepacia, the most virulent, and B. multivorans, the most frequently acquired. Seven proteins were identified in both species, but only two were common to all four strains, linocin and OmpW. Both proteins were selected based on previously reported data on these proteins in other species. Escherichia coli strains expressing recombinant linocin and OmpW showed enhanced attachment (4.2- and 3.9-fold) to lung cells compared to the control, confirming that both proteins are involved in host cell attachment. Immunoproteomic analysis using serum from Bcc-colonized CF patients confirmed that both proteins elicit potent humoral responses in vivo Mice immunized with either recombinant linocin or OmpW were protected from B. cenocepacia and B. multivorans challenge. Both antigens induced potent antigen-specific antibody responses and stimulated strong cytokine responses. In conclusion, our approach identified adhesins that induced excellent protection against two Bcc species and are promising vaccine candidates for a multisubunit vaccine. Furthermore, this study highlights the potential of our proteomics approach to identify potent antigens against other difficult pathogens.

Morphine compromises bronchial epithelial TLR2/IL17R signaling crosstalk, necessary for lung IL17 homeostasis.

Opportunistic lung infection and inflammation is a hallmark of chronic recreational/clinical use of morphine. We show that early induction of IL17 from the bronchial epithelium, following pathogenic encounter is a protective response, which contributes to pathogenic clearance and currently attributed to TLR2 activation in immune cells. Concurrent activation of TLR2 and IL17R in bronchial epithelium results in the sequestration of MyD88 (TLR2 adapter) by Act1/CIKS (IL17R adapter), thereby turning off TLR2 signaling to restore homeostasis. Morphine inhibits the early IL17 release and interaction between Act1 and MyD88, leading to decreased pathogenic clearance and sustained inflammation. Hence, we propose that therapeutically targeting either TLR2 or IL17 in bronchial epithelia, in the context of morphine, can restore inflammatory homeostasis.

Successful Lung Retransplantation in a Patient With Acute Fibrinous and Organizing Pneumonia: A Case Report

Acute fibrinous and organizing pneumonia (AFOP) is an unusual histopathologic pattern characterized by the formation of intra-alveolar plugs of fibrin deposition and associated organizing pneumonia. AFOP is considered to be a form of rejection and portends a dismal prognosis. Here, we present the case of a young male patient who initially underwent a double lung transplantation for cystic fibrosis. After 42 months of regular follow-up, he experienced rapidly progressive respiratory failure. Acute rejection and opportunistic lung infections were suspected. The clinical conditions rapidly deteriorated despite treatment with broad-spectrum antibiotics and high-dose steroids. Therefore, AFOP was suspected owing to: 1) acute clinical presentation; 2) pulmonary computerized tomographic data; 3) typical histopathologic findings on transbronchial biopsieseconds, and 4) lack of response to different treatments. The patient required an emergency bilateral lung retransplantation 44 months after the initial transplantation. The histopathologic analysis of the explanted lungs confirmed the diagnosis of AFOP. Two years after the 2nd transplant, the patient is alive and well. To the best of our knowledge, this is the 1st case of a patient experiencing AFOP following lung transplantation who was successfully rescued by a 2nd bilateral lung retransplantation.

Opportunistic lung infections as a manifestation of Good's syndrome

Good’s syndrome is an acquired immunodeficiency state associated with thymoma. It is characterized by recurrent infection, autoimmune disease, and immunologic abnormality. The insufficient immunity can be managed by intravenous immunoglobulin (IVIG) replacement therapy. We describe 2 patients who presented with Pneumocystis jiroveci pneumonia and Cytomegalovirus pneumonia after thymectomy for a thymoma. Immunologic study revealed hypogammaglobulinemia with very low B-cell count, consistent with Good’s syndrome. They were successfully treated with trimethoprim/sulfamethoxazole and gancyclovir respectively, and they are all well without additional infections, receiving regular IVIG replacement. (Allergy Asthma Respir Dis 2015;3:365-369)

Signature Motifs Identify an Acinetobacter Cif Virulence Factor with Epoxide Hydrolase Activity

Endocytic recycling of the cystic fibrosis transmembrane conductance regulator (CFTR) is blocked by the CFTR inhibitory factor (Cif). Originally discovered in Pseudomonas aeruginosa, Cif is a secreted epoxide hydrolase that is transcriptionally regulated by CifR, an epoxide-sensitive repressor. In this report, we investigate a homologous protein found in strains of the emerging nosocomial pathogens Acinetobacter nosocomialis and Acinetobacter baumannii ("aCif"). Like Cif, aCif is an epoxide hydrolase that carries an N-terminal secretion signal and can be purified from culture supernatants. When applied directly to polarized airway epithelial cells, mature aCif triggers a reduction in CFTR abundance at the apical membrane. Biochemical and crystallographic studies reveal a dimeric assembly with a stereochemically conserved active site, confirming our motif-based identification of candidate Cif-like pathogenic EH sequences. Furthermore, cif expression is transcriptionally repressed by a CifR homolog ("aCifR") and is induced in the presence of epoxides. Overall, this Acinetobacter protein recapitulates the essential attributes of the Pseudomonas Cif system and thus may facilitate airway colonization in nosocomial lung infections.

Pulmonary manifestations of Crohn’s disease

Crohn's disease (CD) is a systemic illness with a constellation of extraintestinal manifestations affecting various organs. Of these extraintestinal manifestations of CD, those involving the lung are relatively rare. However, there is a wide array of lung manifestations, ranging from subclinical alterations, airway diseases and lung parenchymal diseases to pleural diseases and drug-related diseases. The most frequent manifestation is bronchial inflammation and suppuration with or without bronchiectasis. Bronchoalveolar lavage findings show an increased percentage of neutrophils. Drug-related pulmonary abnormalities include disorders which are directly induced by sulfasalazine, mesalamine and methotrexate, and opportunistic lung infections due to immunosuppressive treatment. In most patients, the development of pulmonary disease parallels that of intestinal disease activity. Although infrequent, clinicians dealing with CD must be aware of these, sometimes life-threatening, conditions to avoid further impairment of health status and to alleviate patient symptoms by prompt recognition and treatment. The treatment of CD-related respiratory disorders depends on the specific pattern of involvement, and in most patients, steroids are required in the initial management.

Unusual coexistence of opportunistic lung infections in a human immunodeficiency virus positive patient suffering from persistent Pneumocystis jirovecii pneumonia: A case report

It is well-established that HIV patients are at high risk of opportunistic infections (OI), like the ones caused by Pneumocystis jirovecii, a worldwide pathogen implicated in interstitial pneumonia (PcP). We present a case of a newly diagnosed HIV-1 patient with multiple OI, including a persistent form of PcP, an invasive aspergillosis (IA), cytomegalovirus and Mycobacterium xenopi lung infection. We describe the combination of laboratorial screening, surgery and antimicrobial therapy which were crucial for patient recovery.

Burkholderia multivorans survival and trafficking within macrophages

Cystic fibrosis (CF) patients are at great risk of opportunistic lung infection, particularly by members of the Burkholderia cepacia complex (Bcc). This group of bacteria can cause damage to the lung tissue of infected patients and are difficult to eradicate due to their high levels of antibiotic resistance. Although the highly virulent Burkholderia cenocepacia has been the focus of virulence research for the past decade, Burkholderia multivorans is emerging as the most prevalent Bcc species infecting CF patients in North America. Despite several studies detailing the intramacrophage trafficking and survival of B. cenocepacia, no such data exist for B. multivorans. The results of this study demonstrated that the clinical CF isolates C5568 and C0514 and an environmental B. multivorans isolate, ATCC 17616, were able to replicate and survive within murine macrophages in a manner similar to that of B. cenocepacia strain K56-2. These strains were also able to survive but were unable to replicate within human THP-1 macrophages. Differences in macrophage uptake were observed among all three B. multivorans strains; these variances were attributed to major differences in O-antigen production. Unlike B. cenocepacia-containing vacuoles, which delay phagosomal maturation in murine macrophages by 6 h, all B. multivorans-containing vacuoles co-localized with lysosome-associated membrane protein-1, a late endosome/lysosomal marker, and the lysosomal marker dextran within 2 h of uptake. Together, these results indicated that, whilst both Bcc species were able to survive and replicate within macrophages, they utilized different intramacrophage survival strategies. To observe differences in virulence, the strains were compared using the Galleria mellonella (wax worm) model. When compared with the B. multivorans strains tested, B. cenocepacia K56-2 was highly virulent in this model and killed all worms within 24 h when injected at 10(7) c.f.u. B. multivorans clinical isolates C5568 and C0514 were significantly more virulent than the soil isolate ATCC 17616, which was avirulent even when worms were injected with 10(7) c.f.u. These results suggest strain differences in the virulence of B. multivorans isolates.

Akt-Mediated Proinflammatory Response of Mononuclear Phagocytes Infected with Burkholderia cenocepacia Occurs by a Novel GSK3β-Dependent, IκB Kinase-Independent Mechanism

The environmental bacterium Burkholderia cenocepacia causes opportunistic lung infections in immunocompromised individuals, particularly in patients with cystic fibrosis. Infections in these patients are associated with exacerbated inflammation leading to rapid decay of lung function, and in some cases resulting in cepacia syndrome, which is characterized by a fatal acute necrotizing pneumonia and sepsis. B. cenocepacia can survive intracellularly in macrophages by altering the maturation of the phagosome, but very little is known on macrophage responses to the intracellular infection. In this study, we have examined the role of the PI3K/Akt signaling pathway in B. cenocepacia-infected monocytes and macrophages. We show that PI3K/Akt activity was required for NF-κB activity and the secretion of proinflammatory cytokines during infection with B. cenocepacia. In contrast to previous observations in epithelial cells infected with other Gram-negative bacteria, Akt did not enhance IκB kinase or NF-κB p65 phosphorylation, but rather inhibited GSK3β, a negative regulator of NF-κB transcriptional activity. This novel mechanism of modulation of NF-κB activity may provide a unique therapeutic target for controlling excessive inflammation upon B. cenocepacia infection.