肺曲霉病患者肺微生物组和转录组特征研究进展_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

孙超 ,  苏欣

南京大学医学院附属鼓楼医院呼吸与危重症医学科（江苏南京 210008）;

Corresponding author：

苏欣, Email: suxinjs@163.com

Keywords：

DOI：

10.7507/1671-6205.202412019

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Citation： 孙超, 苏欣. 肺曲霉病患者肺微生物组和转录组特征研究进展. Chinese Journal of Respiratory and Critical Care Medicine, 2025, 24(9): 665-669. doi: 10.7507/1671-6205.202412019 Copy

1.	El-Baba F, Gao Y, Soubani AO. Pulmonary aspergillosis: what the generalist needs to know. Am J Med, 2020, 133(6): 668-674.
2.	王佳美, 顾彧, 宋梦月, 等. 慢性阻塞性肺疾病合并不同类型肺曲霉病临床研究进展. 中国呼吸与危重监护杂志, 2024, 23(1): 53-59.
3.	Turnbaugh PJ, Ley RE, Hamady M, et al. The human microbiome project. Nature, 2007, 449(7164): 804-810.
4.	Huffnagle GB, Dickson RP, Lukacs NW. The respiratory tract microbiome and lung inflammation: a two-way street. Mucosal Immunol, 2017, 10(2): 299-306.
5.	Li R, Li J, Zhou X. Lung microbiome: new insights into the pathogenesis of respiratory diseases. Signal Transduct Target Ther, 2024, 9(1): 19.
6.	Charlson ES, Diamond JM, Bittinger K, et al. Lung-enriched organisms and aberrant bacterial and fungal respiratory microbiota after lung transplant. Am J Respir Crit Care Med, 2012, 186(6): 536-545.
7.	Kim YG, Udayanga KG, Totsuka N, et al. Gut dysbiosis promotes M2 macrophage polarization and allergic airway inflammation via fungi-induced PGE(2). Cell Host Microbe, 2014, 15(1): 95-102.
8.	Young JC, Chehoud C, Bittinger K, et al. Viral metagenomics reveal blooms of anelloviruses in the respiratory tract of lung transplant recipients. Am J Transplant, 2015, 15(1): 200-209.
9.	Coker OO, Wu WKK, Wong SH, et al. Altered gut archaea composition and interaction with bacteria are associated with colorectal cancer. Gastroenterology, 2020, 159(4): 1459-1470, e5.
10.	Koskinen K, Pausan MR, Perras AK, et al. First Insights into the diverse human archaeome: specific detection of archaea in the gastrointestinal tract, lung, and nose and on skin. mBio, 2017, 8(6): e00824-17.
11.	Uzelac M, Li Y, Chakladar J, et al. Archaea microbiome dysregulated genes and pathways as molecular targets for lung adenocarcinoma and squamous cell carcinoma. Int J Mol Sci, 2022, 23(19): 11566.
12.	Briard B, Bomme P, Lechner BE, et al. Pseudomonas aeruginosa manipulates redox and iron homeostasis of its microbiota partner Aspergillus fumigatus via phenazines. Sci Rep, 2015, 5: 8220.
13.	Briard B, Heddergott C, Latge JP. Volatile compounds emitted by Pseudomonas aeruginosa stimulate growth of the fungal pathogen Aspergillus fumigatus. mBio, 2016, 7(2): e00219.
14.	Briard B, Rasoldier V, Bomme P, et al. Dirhamnolipids secreted from Pseudomonas aeruginosa modify anjpegungal susceptibility of Aspergillus fumigatus by inhibiting beta1, 3 glucan synthase activity. ISME J, 2017, 11(7): 1578-1591.
15.	Karimi K, Inman MD, Bienenstock J, et al. Lactobacillus reuteri-induced regulatory T cells protect against an allergic airway response in mice. Am J Respir Crit Care Med, 2009, 179(3): 186-193.
16.	MacSharry J, O'Mahony C, Shalaby KH, et al. Immunomodulatory effects of feeding with Bifidobacterium longum on allergen-induced lung inflammation in the mouse. Pulm Pharmacol Ther, 2012, 25(4): 325-334.
17.	Bacher P, Hohnstein T, Beerbaum E, et al. Human Anti-fungal Th17 immunity and pathology rely on cross-reactivity against Candida albicans. Cell, 2019, 176(6): 1340-1355, e15.
18.	Steele C, Rapaka RR, Metz A, et al. The beta-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatus. PLoS Pathog, 2005, 1(4): e42.
19.	Seelbinder B, Wallstabe J, Marischen L, et al. Triple RNA-Seq reveals synergy in a human virus-fungus co-infection model. Cell Rep, 2020, 33(7): 108389.
20.	Singanayagam A, Glanville N, Cuthbertson L, et al. Inhaled corticosteroid suppression of cathelicidin drives dysbiosis and bacterial infection in chronic obstructive pulmonary disease. Sci Transl Med, 2019, 11(507): eaav3879.
21.	De Baets F, De Keyzer L, Van Daele S, et al. Risk factors and impact of allergic bronchopulmonary aspergillosis in Pseudomonas aeruginosa-negative CF patients. Pediatr Allergy Immunol, 2018, 29(7): 726-731.
22.	Hurt W, Youngs J, Ball J, et al. COVID-19-associated pulmonary aspergillosis in mechanically ventilated patients: a prospective, multicentre UK study. Thorax, 2023, 79(1): 75-82.
23.	Zhang H, Ai JW, Yang W, et al. Metatranscriptomic characterization of coronavirus disease 2019 identified a host transcriptional classifier associated with immune signaling. Clin Infect Dis, 2021, 73(3): 376-385.
24.	Feys S, Goncalves SM, Khan M, et al. Lung epithelial and myeloid innate immunity in influenza-associated or COVID-19-associated pulmonary aspergillosis: an observational study. Lancet Respir Med, 2022, 10(12): 1147-1159.
25.	Ao Z, Xu H, Li M, et al. Clinical characteristics, diagnosis, outcomes and lung microbiome analysis of invasive pulmonary aspergillosis in the community-acquired pneumonia patients. BMJ Open Respir Res, 2023, 10(1): e001358.
26.	Herivaux A, Willis JR, Mercier T, et al. Lung microbiota predict invasive pulmonary aspergillosis and its outcome in immunocompromised patients. Thorax, 2022, 77(3): 283-291.
27.	Nunzi E, Renga G, Palmieri M, et al. A shifted composition of the lung microbiota conditions the antifungal response of immunodeficient mice. Int J Mol Sci, 2021, 22(16): 8474.
28.	de Steenhuijsen Piters WA, Huijskens EG, Wyllie AL, et al. Dysbiosis of upper respiratory tract microbiota in elderly pneumonia patients. ISME J, 2016, 10(1): 97-108.
29.	Segal LN, Clemente JC, Tsay JC, et al. Enrichment of the lung microbiome with oral taxa is associated with lung inflammation of a Th17 phenotype. Nat Microbiol, 2016, 1: 16031.
30.	Jorissen J, van den Broek MFL, De Boeck I, et al. Case-control microbiome study of chronic otitis media with effusion in children points at Streptococcus salivarius as a pathobiont-inhibiting species. mSystems, 2021, 6(2): e00056-21.
31.	Cuthbertson L, Felton I, James P, et al. The fungal airway microbiome in cystic fibrosis and non-cystic fibrosis bronchiectasis. J Cyst Fibros, 2021, 20(2): 295-302.
32.	Crossen AJ, Ward RA, Reedy JL, et al. Human airway epithelium responses to invasive fungal infections: a critical partner in innate immunity. J Fungi (Basel), 2022, 9(1): 40.
33.	Morton CO, Varga JJ, Hornbach A, et al. The temporal dynamics of differential gene expression in Aspergillus fumigatus interacting with human immature dendritic cells in vitro. PLoS One, 2011, 6(1): e16016.
34.	Feys S, Vanmassenhove S, Kraisin S, et al. Lower respiratory tract single-cell RNA sequencing and neutrophil extracellular trap profiling of COVID-19-associated pulmonary aspergillosis: a single centre, retrospective, observational study. Lancet Microbe, 2024, 5(3): e247-e260.
35.	Goedhart M, Slot E, Pascutti MF, et al. Bone marrow harbors a unique population of dendritic cells with the potential to boost neutrophil formation upon exposure to fungal antigen. Cells, 2021, 11(1): 55.
36.	Kale SD, Ayubi T, Chung D, et al. Modulation of immune signaling and metabolism highlights host and fungal transcriptional responses in mouse models of invasive pulmonary Aspergillosis. Sci Rep, 2017, 7(1): 17096.
37.	Zoran T, Seelbinder B, White PL, et al. Molecular profiling reveals characteristic and decisive signatures in patients after allogeneic stem cell transplantation suffering from invasive pulmonary aspergillosis. J Fungi (Basel), 2022, 8(2): 171.
38.	Dietschmann A, Schruefer S, Westermann S, et al. Phosphatidylinositol 3-kinase (PI3K) orchestrates Aspergillus fumigatus-induced eosinophil activation independently of canonical toll-like receptor (TLR)/C-type-lectin receptor (CLR) signaling. mBio, 2022, 13(4): e0123922.
39.	Dix A, Czakai K, Springer J, et al. Genome-wide expression profiling reveals S100B as biomarker for invasive aspergillosis. Front Microbiol, 2016, 7: 320.
40.	Umesh M, Singaravelu V, Daulatabad V, et al. An overview of prognostic value of neurologic and cardiac biomarkers in patients with COVID-19 sequelae. Horm Mol Biol Clin Investig, 2022, 43(4): 475-484.
41.	Li H, Liu L, Zhou W, et al. Pentraxin 3 in bronchoalveolar lavage fluid and plasma in non-neutropenic patients with pulmonary aspergillosis. Clin Microbiol Infect, 2019, 25(4): 504-510.
42.	Luo RG, Wu YF, Lu HW, et al. Th2-skewed peripheral T-helper cells drive B-cells in allergic bronchopulmonary aspergillosis. Eur Respir J, 2024, 63(5): 2400386.
43.	Kalantar KL, Neyton L, Abdelghany M, et al. Integrated host-microbe plasma metagenomics for sepsis diagnosis in a prospective cohort of critically ill adults. Nat Microbiol, 2022, 7(11): 1805-1816.
44.	Costantini C, Nunzi E, Spolzino A, et al. A high-risk profile for invasive fungal infections is associated with altered nasal microbiota and niche determinants. Infect Immun, 2022, 90(4): e0004822.
45.	Wilck N, Matus MG, Kearney SM, et al. Salt-responsive gut commensal modulates T(H)17 axis and disease. Nature, 2017, 551(7682): 585-589.
46.	McAleer JP, Nguyen NL, Chen K, et al. Pulmonary Th17 antifungal immunity is regulated by the gut microbiome. J Immunol, 2016, 197(1): 97-107.
47.	Chakraborty K, Raundhal M, Chen BB, et al. The mito-DAMP cardiolipin blocks IL-10 production causing persistent inflammation during bacterial pneumonia. Nat Commun, 2017, 8: 13944.
48.	Assing K, Laursen CB, Campbell AJ, et al. Proteome and dihydrorhodamine profiling of bronchoalveolar lavage in patients with chronic pulmonary aspergillosis. J Fungi (Basel), 2024, 10(5): 314.
49.	Machata S, Muller MM, Lehmann R, et al. Proteome analysis of bronchoalveolar lavage fluids reveals host and fungal proteins highly expressed during invasive pulmonary aspergillosis in mice and humans. Virulence, 2020, 11(1): 1337-1351.

1. El-Baba F, Gao Y, Soubani AO. Pulmonary aspergillosis: what the generalist needs to know. Am J Med, 2020, 133(6): 668-674.
2. 王佳美, 顾彧, 宋梦月, 等. 慢性阻塞性肺疾病合并不同类型肺曲霉病临床研究进展. 中国呼吸与危重监护杂志, 2024, 23(1): 53-59.
3. Turnbaugh PJ, Ley RE, Hamady M, et al. The human microbiome project. Nature, 2007, 449(7164): 804-810.
4. Huffnagle GB, Dickson RP, Lukacs NW. The respiratory tract microbiome and lung inflammation: a two-way street. Mucosal Immunol, 2017, 10(2): 299-306.
5. Li R, Li J, Zhou X. Lung microbiome: new insights into the pathogenesis of respiratory diseases. Signal Transduct Target Ther, 2024, 9(1): 19.
6. Charlson ES, Diamond JM, Bittinger K, et al. Lung-enriched organisms and aberrant bacterial and fungal respiratory microbiota after lung transplant. Am J Respir Crit Care Med, 2012, 186(6): 536-545.
7. Kim YG, Udayanga KG, Totsuka N, et al. Gut dysbiosis promotes M2 macrophage polarization and allergic airway inflammation via fungi-induced PGE(2). Cell Host Microbe, 2014, 15(1): 95-102.
8. Young JC, Chehoud C, Bittinger K, et al. Viral metagenomics reveal blooms of anelloviruses in the respiratory tract of lung transplant recipients. Am J Transplant, 2015, 15(1): 200-209.
9. Coker OO, Wu WKK, Wong SH, et al. Altered gut archaea composition and interaction with bacteria are associated with colorectal cancer. Gastroenterology, 2020, 159(4): 1459-1470, e5.
10. Koskinen K, Pausan MR, Perras AK, et al. First Insights into the diverse human archaeome: specific detection of archaea in the gastrointestinal tract, lung, and nose and on skin. mBio, 2017, 8(6): e00824-17.
11. Uzelac M, Li Y, Chakladar J, et al. Archaea microbiome dysregulated genes and pathways as molecular targets for lung adenocarcinoma and squamous cell carcinoma. Int J Mol Sci, 2022, 23(19): 11566.
12. Briard B, Bomme P, Lechner BE, et al. Pseudomonas aeruginosa manipulates redox and iron homeostasis of its microbiota partner Aspergillus fumigatus via phenazines. Sci Rep, 2015, 5: 8220.
13. Briard B, Heddergott C, Latge JP. Volatile compounds emitted by Pseudomonas aeruginosa stimulate growth of the fungal pathogen Aspergillus fumigatus. mBio, 2016, 7(2): e00219.
14. Briard B, Rasoldier V, Bomme P, et al. Dirhamnolipids secreted from Pseudomonas aeruginosa modify anjpegungal susceptibility of Aspergillus fumigatus by inhibiting beta1, 3 glucan synthase activity. ISME J, 2017, 11(7): 1578-1591.
15. Karimi K, Inman MD, Bienenstock J, et al. Lactobacillus reuteri-induced regulatory T cells protect against an allergic airway response in mice. Am J Respir Crit Care Med, 2009, 179(3): 186-193.
16. MacSharry J, O'Mahony C, Shalaby KH, et al. Immunomodulatory effects of feeding with Bifidobacterium longum on allergen-induced lung inflammation in the mouse. Pulm Pharmacol Ther, 2012, 25(4): 325-334.
17. Bacher P, Hohnstein T, Beerbaum E, et al. Human Anti-fungal Th17 immunity and pathology rely on cross-reactivity against Candida albicans. Cell, 2019, 176(6): 1340-1355, e15.
18. Steele C, Rapaka RR, Metz A, et al. The beta-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatus. PLoS Pathog, 2005, 1(4): e42.
19. Seelbinder B, Wallstabe J, Marischen L, et al. Triple RNA-Seq reveals synergy in a human virus-fungus co-infection model. Cell Rep, 2020, 33(7): 108389.
20. Singanayagam A, Glanville N, Cuthbertson L, et al. Inhaled corticosteroid suppression of cathelicidin drives dysbiosis and bacterial infection in chronic obstructive pulmonary disease. Sci Transl Med, 2019, 11(507): eaav3879.
21. De Baets F, De Keyzer L, Van Daele S, et al. Risk factors and impact of allergic bronchopulmonary aspergillosis in Pseudomonas aeruginosa-negative CF patients. Pediatr Allergy Immunol, 2018, 29(7): 726-731.
22. Hurt W, Youngs J, Ball J, et al. COVID-19-associated pulmonary aspergillosis in mechanically ventilated patients: a prospective, multicentre UK study. Thorax, 2023, 79(1): 75-82.
23. Zhang H, Ai JW, Yang W, et al. Metatranscriptomic characterization of coronavirus disease 2019 identified a host transcriptional classifier associated with immune signaling. Clin Infect Dis, 2021, 73(3): 376-385.
24. Feys S, Goncalves SM, Khan M, et al. Lung epithelial and myeloid innate immunity in influenza-associated or COVID-19-associated pulmonary aspergillosis: an observational study. Lancet Respir Med, 2022, 10(12): 1147-1159.
25. Ao Z, Xu H, Li M, et al. Clinical characteristics, diagnosis, outcomes and lung microbiome analysis of invasive pulmonary aspergillosis in the community-acquired pneumonia patients. BMJ Open Respir Res, 2023, 10(1): e001358.
26. Herivaux A, Willis JR, Mercier T, et al. Lung microbiota predict invasive pulmonary aspergillosis and its outcome in immunocompromised patients. Thorax, 2022, 77(3): 283-291.
27. Nunzi E, Renga G, Palmieri M, et al. A shifted composition of the lung microbiota conditions the antifungal response of immunodeficient mice. Int J Mol Sci, 2021, 22(16): 8474.
28. de Steenhuijsen Piters WA, Huijskens EG, Wyllie AL, et al. Dysbiosis of upper respiratory tract microbiota in elderly pneumonia patients. ISME J, 2016, 10(1): 97-108.
29. Segal LN, Clemente JC, Tsay JC, et al. Enrichment of the lung microbiome with oral taxa is associated with lung inflammation of a Th17 phenotype. Nat Microbiol, 2016, 1: 16031.
30. Jorissen J, van den Broek MFL, De Boeck I, et al. Case-control microbiome study of chronic otitis media with effusion in children points at Streptococcus salivarius as a pathobiont-inhibiting species. mSystems, 2021, 6(2): e00056-21.
31. Cuthbertson L, Felton I, James P, et al. The fungal airway microbiome in cystic fibrosis and non-cystic fibrosis bronchiectasis. J Cyst Fibros, 2021, 20(2): 295-302.
32. Crossen AJ, Ward RA, Reedy JL, et al. Human airway epithelium responses to invasive fungal infections: a critical partner in innate immunity. J Fungi (Basel), 2022, 9(1): 40.
33. Morton CO, Varga JJ, Hornbach A, et al. The temporal dynamics of differential gene expression in Aspergillus fumigatus interacting with human immature dendritic cells in vitro. PLoS One, 2011, 6(1): e16016.
34. Feys S, Vanmassenhove S, Kraisin S, et al. Lower respiratory tract single-cell RNA sequencing and neutrophil extracellular trap profiling of COVID-19-associated pulmonary aspergillosis: a single centre, retrospective, observational study. Lancet Microbe, 2024, 5(3): e247-e260.
35. Goedhart M, Slot E, Pascutti MF, et al. Bone marrow harbors a unique population of dendritic cells with the potential to boost neutrophil formation upon exposure to fungal antigen. Cells, 2021, 11(1): 55.
36. Kale SD, Ayubi T, Chung D, et al. Modulation of immune signaling and metabolism highlights host and fungal transcriptional responses in mouse models of invasive pulmonary Aspergillosis. Sci Rep, 2017, 7(1): 17096.
37. Zoran T, Seelbinder B, White PL, et al. Molecular profiling reveals characteristic and decisive signatures in patients after allogeneic stem cell transplantation suffering from invasive pulmonary aspergillosis. J Fungi (Basel), 2022, 8(2): 171.
38. Dietschmann A, Schruefer S, Westermann S, et al. Phosphatidylinositol 3-kinase (PI3K) orchestrates Aspergillus fumigatus-induced eosinophil activation independently of canonical toll-like receptor (TLR)/C-type-lectin receptor (CLR) signaling. mBio, 2022, 13(4): e0123922.
39. Dix A, Czakai K, Springer J, et al. Genome-wide expression profiling reveals S100B as biomarker for invasive aspergillosis. Front Microbiol, 2016, 7: 320.
40. Umesh M, Singaravelu V, Daulatabad V, et al. An overview of prognostic value of neurologic and cardiac biomarkers in patients with COVID-19 sequelae. Horm Mol Biol Clin Investig, 2022, 43(4): 475-484.
41. Li H, Liu L, Zhou W, et al. Pentraxin 3 in bronchoalveolar lavage fluid and plasma in non-neutropenic patients with pulmonary aspergillosis. Clin Microbiol Infect, 2019, 25(4): 504-510.
42. Luo RG, Wu YF, Lu HW, et al. Th2-skewed peripheral T-helper cells drive B-cells in allergic bronchopulmonary aspergillosis. Eur Respir J, 2024, 63(5): 2400386.
43. Kalantar KL, Neyton L, Abdelghany M, et al. Integrated host-microbe plasma metagenomics for sepsis diagnosis in a prospective cohort of critically ill adults. Nat Microbiol, 2022, 7(11): 1805-1816.
44. Costantini C, Nunzi E, Spolzino A, et al. A high-risk profile for invasive fungal infections is associated with altered nasal microbiota and niche determinants. Infect Immun, 2022, 90(4): e0004822.
45. Wilck N, Matus MG, Kearney SM, et al. Salt-responsive gut commensal modulates T(H)17 axis and disease. Nature, 2017, 551(7682): 585-589.
46. McAleer JP, Nguyen NL, Chen K, et al. Pulmonary Th17 antifungal immunity is regulated by the gut microbiome. J Immunol, 2016, 197(1): 97-107.
47. Chakraborty K, Raundhal M, Chen BB, et al. The mito-DAMP cardiolipin blocks IL-10 production causing persistent inflammation during bacterial pneumonia. Nat Commun, 2017, 8: 13944.
48. Assing K, Laursen CB, Campbell AJ, et al. Proteome and dihydrorhodamine profiling of bronchoalveolar lavage in patients with chronic pulmonary aspergillosis. J Fungi (Basel), 2024, 10(5): 314.
49. Machata S, Muller MM, Lehmann R, et al. Proteome analysis of bronchoalveolar lavage fluids reveals host and fungal proteins highly expressed during invasive pulmonary aspergillosis in mice and humans. Virulence, 2020, 11(1): 1337-1351.

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肺曲霉病患者肺微生物组和转录组特征研究进展

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