pulmonary granulomas
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2022 ◽  
Vol 2022 ◽  
pp. 1-4
Author(s):  
Masashi Ito ◽  
Akihiro Yoshii ◽  
Takashi Osaki ◽  
Tomohito Kuwako ◽  
Ei Yamaki ◽  
...  

The space around the staple line after lung surgery is at high risk of nontuberculosis Mycobacterium pulmonary disease (NTM-PD). Solitary nodules of NTM-PD around the staple line are difficult to distinguish from lung cancer. There is no clear identification from laboratory data and radiologic findings without histological examination. In the present case, we misdiagnosed the pulmonary granulomas with Mycobacterium avium complex pulmonary disease (MAC-PD) as a recurrence of lung cancer. We conducted radiation therapy. The pulmonary granulomas with MAC-PD were exacerbated by irradiation. The effects of radiation therapy for MAC-PD are unknown. When radiation therapy is performed for the patient coexistence with MAC-PD, we should pay attention to exacerbation of MAC-PD.


2022 ◽  
Vol 12 ◽  
Author(s):  
Laura Hunter ◽  
Suzie Hingley-Wilson ◽  
Graham R. Stewart ◽  
Sally A. Sharpe ◽  
Francisco Javier Salguero

Non-human primate models of Tuberculosis (TB) are one of the most commonly used within the experimental TB field because they closely mimic the whole spectrum of disease progression of human TB. However, the early cellular interactions of the pulmonary granuloma are still not well understood. The use of this model allows investigation into the early interactions of cells within pulmonary granulomas which cannot be undertaken in human samples. Pulmonary granulomas from rhesus and cynomolgus macaques from two timepoints post infection were categorised into categories 1 – 6 (early to late stage granulomas) and immunohistochemistry was used to identify CD68+ macrophages, CD3+ T cells and CD20+ B cells. Multinucleated giant cells and acid-fast bacilli were also quantified. At week four post infection, cynomolgus macaques were found to have more CD68+ cells than rhesus in all but category 1 granulomas. Cynomolgus also had a significantly higher percentage of CD20+ B cells in category 1 granulomas. At week twelve post infection, CD68+ cells were most abundant in category 4 and 5 granulomas in both species; however, there were no significant differences between them. CD3+ T cells and CD20+ B cells were significantly higher in the majority of granuloma categories in cynomolgus compared to rhesus. Multinucleated giant cells and acid-fast bacilli were most abundant in categories 5 and 6 at week 12 post challenge in both species. This study has identified the basic cellular composition and spatial distribution of immune cells within pulmonary granulomas in both rhesus and cynomolgus macaques over time. The data from this study will add to the knowledge already gained in this field and may inform future research on vaccines and therapeutics for TB.


2021 ◽  
Author(s):  
Taylor W. Foreman ◽  
Christine E. Nelson ◽  
Keith D. Kauffman ◽  
Nickiana E. Lora ◽  
Caian L. Vinhaes ◽  
...  

The HIV-mediated decline in circulating CD4 T cells correlates with increased the risk of active tuberculosis (TB). However, HIV/Mycobacterium tuberculosis (Mtb) co-infected individuals also have an increased incidence of TB prior to loss of CD4 T cells in blood, raising the possibility that HIV co-infection leads to disruption of CD4 T cell responses at the site of lung infection before they are observed systemically. Here we used a rhesus macaque model of SIV/Mtb co-infection to study the early effects of acute SIV infection on CD4 T cells in pulmonary Mtb granulomas. Two weeks after SIV co-infection CD4 T cells were dramatically depleted from granulomas, before significant bacterial outgrowth, disease reactivation as measured by PET-CT imaging, or CD4 T cell loss in blood, airways, and lymph nodes. Mtb-specific CD4 T cells, CCR5-expressing, in granulomas were preferentially depleted by SIV infection. Moreover, CD4 T cells were preferentially depleted from the granuloma core and lymphocyte cuff relative to B cell-rich regions, and live imaging of granuloma explants showed that SIV co-infection reduced T cell motility. Thus, Mtb-specific CD4 T cells in pulmonary granulomas may be decimated before many patients even experience the first symptoms of acute HIV infection.


Author(s):  
Che-Liang Chung ◽  
Wei-Chang Huang ◽  
Hung-Ling Huang ◽  
Chun-Shih Chin ◽  
Meng-Hsuan Cheng ◽  
...  

Abstract Background Histologic diagnosis of granuloma is often considered clinically equivalent to a definite diagnosis of pulmonary tuberculosis (TB) in endemic area. Optimal management of surgically resected granulomatous inflammation in lung with negative mycobacterial culture results, however, remains unclear. Methods From seven medical institutions in northern, middle, and southern Taiwan between January 2010 and December 2018, patients whose surgically resected pulmonary nodule(s) had histological features suggestive of TB but negative microbiological study results and who received no subsequent anti-TB treatment were identified retrospectively. All patients were followed up for 2 years until death or active TB disease was diagnosed. Results A total of 116 patients were enrolled during the study period. Among them, sixty-one patients (52.6%) were clinically asymptomatic, and 36 (31.0%) patients were immunocompromised. Solitary pulmonary nodule accounted for 44 (39.6%) of all cases. The lung nodules were removed by wedge resection in 95 (81.9%), lobectomy in 17 (14.7%), and segmentectomy in 4 (3.4%) patients. The most common histological feature was granulomatous inflammation (n=116, 100%), followed by caseous necrosis (n=39, 33.6%). During follow-up (218.4 patient-years), none of the patients developed active TB. Conclusions In patients with surgically resected culture-negative pulmonary granulomas, the incidence rate of subsequent active TB is low. Watchful monitoring along with regular clinical, radiological, and microbiological follow-up, instead of routine anti-TB treatment, may also be a reasonable option.


2021 ◽  
Author(s):  
Calla L. Telzrow ◽  
Shannon Esher Righi ◽  
Natalia Castro-Lopez ◽  
Althea Campuzano ◽  
Jacob T. Brooks ◽  
...  

Many successful pathogens cause latent infections, remaining dormant within the host for years but retaining the ability to reactivate to cause symptomatic disease. The human opportunistic pathogen Cryptococcus neoformans is a ubiquitous yeast that establishes latent pulmonary infections in immunocompetent individuals upon fungal inhalation from the environment. These latent infections are frequently characterized by granulomas, or foci of chronic inflammation, that contain dormant cryptococcal cells. Immunosuppression causes these granulomas to break down and release viable fungal cells that proliferate, disseminate, and eventually cause lethal cryptococcosis. This course of C. neoformans dormancy and reactivation is understudied due to limited models, as chronic pulmonary granulomas do not typically form in most mouse models of cryptococcal infection. Here, we report that a previously characterized Cryptococcus-specific gene which is required for host-induced cell wall remodeling, MAR1, inhibits murine granuloma formation. Specifically, the mar1Δ loss-of-function mutant strain induces mature pulmonary granulomas at sites of infection dormancy in mice. Our data suggest that the combination of reduced fungal burden and increased immunogenicity of the mar1Δ mutant strain stimulates a host immune response that contains viable fungi within granulomas. Furthermore, we find that the mar1Δ mutant strain has slow growth and hypoxia resistance phenotypes, which may enable fungal persistence within pulmonary granulomas. Together with the conventional primary murine infection model, latent murine infection models will advance our understanding of cryptococcal disease progression and define fungal features important for persistence in the human host.


Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5193
Author(s):  
Foteinos-Ioannis Dimitrakopoulos ◽  
Anastasia E. Kottorou ◽  
Kristen Rodgers ◽  
John Timothy Sherwood ◽  
Georgia-Angeliki Koliou ◽  
...  

Recently, the role of exosomes in the progression of both cancer and HIV (human immunodeficiency virus) has been described. This study investigates the clinical significance of CD9-positive plasma exosomes in lung cancer patients, healthy individuals, and HIV-positive patients with or without lung cancer. Using a verified with transmission electron microscopy double-sandwich ELISA technique, plasma-derived exosomes were isolated and quantified from 210 lung cancer patients (including 44 metastatic patients with progressive disease after chemotherapy), 49 healthy controls, 20 patients with pulmonary granulomas, 19 HIV+ patients with lung cancer, 31 HIV+ patients without cancer, and 3 HIV+ patients with pulmonary granulomas. Plasma exosome concentrations differed between healthy controls, patients with immunocompetent pulmonary granulomas and patients with lung cancer even after chemotherapy (p < 0.001). Lung cancer patients after chemotherapy had lower exosome concentrations compared to patients with untreated lung cancer or granuloma (p < 0.001 for both). HIV+ patients without lung cancer had significantly higher exosome concentrations compared to HIV+ patients with lung cancer (p = 0.016). Although exosome concentrations differed between all different lung cancer histologies and healthy controls (p < 0.001 for all histologies), adjusted statistical significance was oµy retained for patients with granulomas and SCLC (Small-cell lung cancer, p < 0.001). HIV-induced immunodeficient patients with or without lung cancer had lower plasma exosomes compared to immunocompetent granuloma and lung cancer patients (p < 0.001). Finally, higher plasma exosomes were associated both on univariate (p = 0.044), and multivariate analysis (p = 0.040) with a better 3-year survival in stage II and III NSCLC (Non-small-cell lung carcinoma) patients. In conclusion, our study shows that CD9-positive plasma exosomes are associated with both lung cancer and HIV, prior chemotherapy, as well as with survival, suggesting a possible prognostic value.


2021 ◽  
Vol 8 ◽  
Author(s):  
Mitchell V. Palmer ◽  
Tyler C. Thacker ◽  
Carly Kanipe ◽  
Paola M. Boggiatto

Mycobacterium bovis is the cause of tuberculosis in most animals, most notably cattle. The stereotypical lesion of bovine tuberculosis is the granuloma; a distinct morphological lesion where host and pathogen interact and disease outcome (i.e., dissemination, confinement, or resolution) is determined. Accordingly, it is critical to understand host-pathogen interactions at the granuloma level. Host-pathogen interactions within individual granulomas at different stages of disease have not been examined in cattle. We examined bacterial burden and cytokine expression in individual pulmonary granulomas from steers at 30, 90, 180, and 270 days after experimental aerosol infection with M. bovis. Bacterial burdens within individual granulomas examined 30 days after infection were greater and more heterogenous (variable) than those examined 90 to 270 days after infection. Bacterial burdens did not correlate with expression of IFN-γ, TNF-α, TGF-β, granuloma stage, or lung lesion score, although there was a modest positive correlation with IL-10 expression. Granuloma stage did have modest positive and negative correlations with TNF-α and IL-10, respectively. Heterogeneity and mean expression of IFN-γ, IL-10 and TNF-α did not differ significantly over time, however, expression of TGF-β at 90 days was significantly greater than that seen at 30 days after infection.


Author(s):  
Aasem Abu Shtaya ◽  
Shai Cohen ◽  
Yana Kogan ◽  
Michal Shteinberg ◽  
Ori Sagol

Crohn’s disease is a chronic inflammatory bowel disease that can affect any part of the GI tract, which is frequently associated with extra-intestinal manifestations. Pulmonary parenchymal disease is very uncommon and usually considered to be debilitating and harder to diagnose. Pulmonary granulomas are rarely described in the literature as a complication of Crohn’s disease. Here, we present a patient with Crohn’s disease exacerbation who developed granulomatous lung disease under treatment with vedolizumab. Our case may add evidence to the emerging theory that gut-selective biologic agents could lead to upregulation of some pro-inflammatory factors leading to the evolution of pulmonary disease.


npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Andrew D. White ◽  
Laura Sibley ◽  
Charlotte Sarfas ◽  
Alexandra Morrison ◽  
Jennie Gullick ◽  
...  

AbstractA single intradermal vaccination with MTBVAC given to adult rhesus macaques was well tolerated and conferred a significant improvement in outcome following aerosol exposure to M. tuberculosis compared to that provided by a single BCG vaccination. Vaccination with MTBVAC resulted in a significant reduction in M. tuberculosis infection-induced disease pathology measured using in vivo medical imaging, in gross pathology lesion counts and pathology scores recorded at necropsy, the frequency and severity of pulmonary granulomas and the frequency of recovery of viable M. tuberculosis from extrapulmonary tissues following challenge. The immune profiles induced following immunisation with MTBVAC reflect those identified in human clinical trials of MTBVAC. Evaluation of MTBVAC- and TB peptide-pool-specific T-cell cytokine production revealed a predominantly Th1 response from poly- (IFN-γ+TNF-α+IL2+) and multi-(IFN-γ+TNF-α+) functional CD4 T cells, while only low levels of Th22, Th17 and cytokine-producing CD8 T-cell populations were detected together with low-level, but significant, increases in CFP10-specific IFN-γ secreting cells. In this report, we describe concordance between immune profiles measured in clinical trials and a macaque pre-clinical study demonstrating significantly improved outcome after M. tuberculosis challenge as evidence to support the continued development of MTBVAC as an effective prophylactic vaccine for TB vaccination campaigns.


Thorax ◽  
2020 ◽  
pp. thoraxjnl-2020-216506
Author(s):  
Li-Ta Keng ◽  
Wei-Yung Lo ◽  
Hsien-Neng Huang ◽  
Huan-Jang Ko ◽  
Sheng-Kai Liang
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