scholarly journals Alveolitis in severe SARS-CoV-2 pneumonia is driven by self-sustaining circuits between infected alveolar macrophages and T cells

Author(s):  
Rogan A. Grant ◽  
Luisa Morales-Nebreda ◽  
Nikolay S. Markov ◽  
Suchitra Swaminathan ◽  
Estefany R. Guzman ◽  
...  

AbstractSome patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) develop severe pneumonia and the acute respiratory distress syndrome (ARDS) [1]. Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from other types of pneumonia [2]. We collected bronchoalveolar lavage fluid samples from 86 patients with SARS-CoV-2-induced respiratory failure and 252 patients with known or suspected pneumonia from other pathogens and subjected them to flow cytometry and bulk transcriptomic profiling. We performed single cell RNA-Seq in 5 bronchoalveolar lavage fluid samples collected from patients with severe COVID-19 within 48 hours of intubation. In the majority of patients with SARS-CoV-2 infection at the onset of mechanical ventilation, the alveolar space is persistently enriched in alveolar macrophages and T cells without neutrophilia. Bulk and single cell transcriptomic profiling suggest SARS-CoV-2 infects alveolar macrophages that respond by recruiting T cells. These T cells release interferon-gamma to induce inflammatory cytokine release from alveolar macrophages and further promote T cell recruitment. Our results suggest SARS-CoV-2 causes a slowly unfolding, spatially-limited alveolitis in which alveolar macrophages harboring SARS-CoV-2 transcripts and T cells form a positive feedback loop that drives progressive alveolar inflammation.This manuscript is accompanied by an online resource: https://www.nupulmonary.org/covid-19/One sentence summarySARS-CoV-2-infected alveolar macrophages form positive feedback loops with T cells in patients with severe COVID-19.

2022 ◽  
Vol 38 (3) ◽  
Author(s):  
Xiaoying Li ◽  
Zinan Jiang

Objectives: To assess the association of bronchoalveolar lavage fluid (BALF) α-SMA and ß-catenin levels and the severity of pneumonia. Methods: The records of patients with severe pneumonia treated in our hospital from June 2019 to June 2020 were selected. The clinical outcome was observed within 10 days. For the purpose of analysis, patients were divided into two groups according to the outcome, 47 cases in the improvement group and 39 cases in the deterioration group. The intubation time, mechanical ventilation time and APACHE II score 10 days after admission were compared between the two groups; We assessed pulmonary infections using the clinical pulmonary infection score(CPIS). The levels of α-SMA and ß-catenin in bronchoalveolar lavage fluid at different time points were compared and analyzed, to analyze the association between the levels and the CPIS. Results: The APACHE II score in the improvement group were lower than those in the deterioration group (P<0.05). The expressions of α-SMA and ß-catenin in the BALF of patients in the improvement group were significantly lower than those of patients in the deterioration group on day 1, 3, and 7 (P<0.05); and the expressions of α-SMA and ß-catenin in the BALF of patients in the improvement group decreased with time, while those of patients in the deterioration group increased gradually with time(P<0.05). The expressions of α-SMA and ß-catenin in patients with CPIS>6 was significantly higher than those in patients with CPI≤6(P<0.05). Pearson correlation analysis showed that the levels of α-SMA and ß-catenin in BALF were positively correlated with the CPIS. Conclusion: The levels of α-SMA and ß-catenin in BALF are closely associated with the clinical condition of patients with severe pneumonia; the levels are positively associated with the severity of the disease and they increase with symptomatic worsening. doi: https://doi.org/10.12669/pjms.38.3.5329 How to cite this:Li X, Jiang Z. Correlation between α-SMA and ß-catenin levels in bronchoalveolar lavage fluid and severity of pneumonia. Pak J Med Sci. 2022;38(3):---------. doi: https://doi.org/10.12669/pjms.38.3.5329 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


2014 ◽  
Vol 33 (4) ◽  
pp. S300 ◽  
Author(s):  
J.R. Greenland ◽  
C.M. Wong ◽  
R. Ahuja ◽  
M. Gottschall ◽  
N.N. Trivedi ◽  
...  

1993 ◽  
Vol 147 (6_pt_1) ◽  
pp. 1562-1568 ◽  
Author(s):  
Hideki Takahashi ◽  
Kazumi Ishidoh ◽  
Daisuke Muno ◽  
Akihiko Ohwada ◽  
Toshihiro Nukiwa ◽  
...  

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Lyné van Rensburg ◽  
Johann M. van Zyl ◽  
Johan Smith ◽  
Pierre Goussard

Abstract Background Bronchoalveolar lavage is a useful bronchoscopy technique. However, studies in “normal” children populations are few. Furthermore, the anti-inflammatory effects of exogenous pulmonary surfactants on the bronchoalveolar cellular components are limited. Methods Thirty children, aged 3 to 14 years, underwent diagnostic bronchoscopy and bronchoalveolar lavage. Differential cytology, cytokine and chemokine measurements were performed on the fluid after exogenous surfactant exposure. The aim of the study was to investigate the potential anti-inflammatory effects of exogenous surfactants on the bronchoalveolar lavage fluid, specifically alveolar macrophages of healthy South African children. Results Alveolar macrophages were the predominant cellular population in normal children. Patients with inflammatory pneumonopathies had significantly more neutrophils. Levels of inflammatory cytokines were significantly lower after exogenous surfactant exposure. Moreover, IL-10 and IL-12 cytokine secretion increased after exogenous surfactant exposure. Conclusion This study provides the first data on bronchoalveolar lavage of healthy South African children. Bronchoalveolar lavage fluid from patients with pulmonary inflammation was characterised by neutrophilia. Finally, we propose that exogenous surfactant treatment could help alleviate inflammation in diseased states where it occurs in the tracheobronchial tree.


2004 ◽  
Vol 11 (4) ◽  
pp. 795-798 ◽  
Author(s):  
E. C. Soethout ◽  
K. E. Müller ◽  
A. J. M. van den Belt ◽  
V. P. M. G. Rutten

ABSTRACT A method is proposed to identify leukocyte subpopulations in bovine bronchoalveolar lavage fluid by dual-laser flow cytometry. The technique uses several parameters, i.e., exclusion of highly autofluorescent alveolar macrophages and inclusion of leukocytes on the basis of labeling by specific antibodies and light scatter characteristics.


2010 ◽  
Vol 84 (17) ◽  
pp. 8790-8798 ◽  
Author(s):  
Debbie C. P. Lee ◽  
James A. E. Harker ◽  
John S. Tregoning ◽  
Sowsan F. Atabani ◽  
Cecilia Johansson ◽  
...  

ABSTRACT Regulatory CD4+ T cells have been shown to be important in limiting immune responses, but their role in respiratory viral infections has received little attention. Here we observed that following respiratory syncytial virus (RSV) infection, CD4+ Foxp3+ CD25+ natural regulatory T-cell numbers increased in the bronchoalveolar lavage fluid, lung, mediastinal lymph nodes, and spleen. The depletion of CD25+ natural regulatory T cells prior to RSV infection led to enhanced weight loss with delayed recovery that was surprisingly accompanied by increased numbers of activated natural killer cells in the lung and bronchoalveolar lavage fluid on day 8 postinfection. Increased numbers of neutrophils were also detected within the bronchoalveolar lavage fluid and correlated with elevated levels of myeloperoxidase as well as interleukin-6 (IL-6) and gamma interferon (IFN-γ). CD25+ natural regulatory T-cell depletion also led to enhanced numbers of proinflammatory T cells producing IFN-γ and tumor necrosis factor alpha (TNF-α) in the lung. Despite these increases in inflammatory responses and disease severity, the viral load was unaltered. This work highlights a critical role for natural regulatory T cells in regulating the adaptive and innate immune responses during the later stages of lung viral infections.


Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1231
Author(s):  
Yasuaki Kotetsu ◽  
Toyoshi Yanagihara ◽  
Kunihiro Suzuki ◽  
Hiroyuki Ando ◽  
Daisuke Eto ◽  
...  

Sarcoidosis is a systemic, granulomatous disease caused by unknown immunological abnormalities. The organs most vulnerable to sarcoidosis are the lungs. Patients often resolve spontaneously, but the lungs can also be severely affected. Although details regarding prognostic factors in sarcoidosis patients with lung involvement remain unclear, several reports have suggested that immune checkpoint molecules are involved in the pathogenesis of sarcoidosis. In this study, we divided sarcoidosis patients into two groups based on chest computed tomography (CT) findings and compared immune checkpoint molecules expressed on T cells in bronchoalveolar lavage fluid (BALF) in the two groups, using flow cytometry. We found elevated programmed cell death 1 (PD-1) or T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) expression on T cells in BALF in patients with spontaneous improvement in CT findings, compared with those in patients without improvement in CT findings. In conclusion, our study implies that PD-1 or TIM-3 expression on T cells in BALF may be a prognostic factor for pulmonary lesions in sarcoidosis.


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