Innate and adaptive immune responses in subjects with CPA secondary to post-pulmonary tuberculosis lung abnormalities
Naresh Kumar Chirumamilla
Department of Internal medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Investigation, Writing - review & editing, Validation, Project administration, Data curation
Search for more papers by this authorKanika Arora
Department of Pediatric immunopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Investigation, Methodology, Formal analysis, Writing - review & editing, Data curation
Search for more papers by this authorMandeep Kaur
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Investigation, Writing - review & editing, Methodology, Formal analysis, Data curation
Search for more papers by this authorRitesh Agarwal
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Investigation, Writing - original draft, Writing - review & editing, Visualization, Validation, Methodology, Software, Formal analysis, Project administration, Resources, Supervision, Data curation
Search for more papers by this authorValliappan Muthu
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Investigation, Writing - review & editing, Validation, Methodology, Supervision, Resources
Search for more papers by this authorAmit Rawat
Department of Pediatric immunopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Investigation, Writing - review & editing, Validation, Methodology, Supervision, Resources
Search for more papers by this authorSahajal Dhooria
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Writing - review & editing, Validation, Visualization, Methodology, Supervision
Search for more papers by this authorKuruswamy Thurai Prasad
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Writing - review & editing, Formal analysis, Visualization, Validation, Methodology, Supervision
Search for more papers by this authorAshutosh Nath Aggarwal
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Writing - review & editing, Visualization, Validation, Methodology, Formal analysis, Supervision
Search for more papers by this authorShivaprakash M. Rudramurthy
Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Investigation, Visualization, Writing - review & editing, Project administration, Supervision, Resources
Search for more papers by this authorArunaloke Chakrabarti
Doodhadhari Burfani Hospital, Haridwar, Uttarakhand, India
Contribution: Resources, Supervision, Writing - review & editing, Visualization, Methodology
Search for more papers by this authorHansraj Choudhary
Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Investigation, Methodology, Validation, Visualization, Writing - review & editing, Data curation
Search for more papers by this authorArnab Pal
Department of Biochemistry, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Investigation, Writing - review & editing, Resources
Search for more papers by this authorCorresponding Author
Inderpaul Singh Sehgal
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Correspondence
Inderpaul Singh Sehgal, Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Sector-12, Chandigarh-160012, India.
Email: [email protected]
Contribution: Conceptualization, Investigation, Funding acquisition, Writing - original draft, Writing - review & editing, Visualization, Validation, Methodology, Software, Formal analysis, Project administration, Resources, Supervision, Data curation
Search for more papers by this authorNaresh Kumar Chirumamilla
Department of Internal medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Investigation, Writing - review & editing, Validation, Project administration, Data curation
Search for more papers by this authorKanika Arora
Department of Pediatric immunopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Investigation, Methodology, Formal analysis, Writing - review & editing, Data curation
Search for more papers by this authorMandeep Kaur
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Investigation, Writing - review & editing, Methodology, Formal analysis, Data curation
Search for more papers by this authorRitesh Agarwal
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Investigation, Writing - original draft, Writing - review & editing, Visualization, Validation, Methodology, Software, Formal analysis, Project administration, Resources, Supervision, Data curation
Search for more papers by this authorValliappan Muthu
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Investigation, Writing - review & editing, Validation, Methodology, Supervision, Resources
Search for more papers by this authorAmit Rawat
Department of Pediatric immunopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Investigation, Writing - review & editing, Validation, Methodology, Supervision, Resources
Search for more papers by this authorSahajal Dhooria
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Writing - review & editing, Validation, Visualization, Methodology, Supervision
Search for more papers by this authorKuruswamy Thurai Prasad
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Writing - review & editing, Formal analysis, Visualization, Validation, Methodology, Supervision
Search for more papers by this authorAshutosh Nath Aggarwal
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Writing - review & editing, Visualization, Validation, Methodology, Formal analysis, Supervision
Search for more papers by this authorShivaprakash M. Rudramurthy
Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Investigation, Visualization, Writing - review & editing, Project administration, Supervision, Resources
Search for more papers by this authorArunaloke Chakrabarti
Doodhadhari Burfani Hospital, Haridwar, Uttarakhand, India
Contribution: Resources, Supervision, Writing - review & editing, Visualization, Methodology
Search for more papers by this authorHansraj Choudhary
Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Investigation, Methodology, Validation, Visualization, Writing - review & editing, Data curation
Search for more papers by this authorArnab Pal
Department of Biochemistry, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Contribution: Investigation, Writing - review & editing, Resources
Search for more papers by this authorCorresponding Author
Inderpaul Singh Sehgal
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
Correspondence
Inderpaul Singh Sehgal, Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Sector-12, Chandigarh-160012, India.
Email: [email protected]
Contribution: Conceptualization, Investigation, Funding acquisition, Writing - original draft, Writing - review & editing, Visualization, Validation, Methodology, Software, Formal analysis, Project administration, Resources, Supervision, Data curation
Search for more papers by this authorNaresh Kumar Chirumamilla and Kanika Arora have contributed equally and may be considered joint first authors.
Abstract
Background
Post-tuberculosis lung abnormality (PTLA) is the most common risk factor for chronic pulmonary aspergillosis (CPA), and 14%–25% of the subjects with PTLA develop CPA. The pathogenesis and the host immune response in subjects with PTLA who develop CPA need to be better understood.
Methods
We prospectively compared the innate and adaptive immune responses mounted by patients of PTLA with or without CPA (controls). We studied the neutrophil oxidative burst (by dihydrorhodamine 123 test), classic (serum C3 and C4 levels) and alternative (mannose-binding lectin [MBL] protein levels) complement pathway, serum immunoglobulins (IgG, IgM and IgA), B and T lymphocytes and their subsets in subjects with PTLA with or without CPA.
Results
We included 111 subjects (58 CPA and 53 controls) in the current study. The mean ± SD age of the study population was 42.6 ± 15.7 years. The cases and controls were matched for age, gender distribution and body weight. Subjects with CPA had impaired neutrophil oxidative burst, lower memory T lymphocytes and impaired Th-1 immune response (lower Th-1 lymphocytes) than controls. We found no significant difference between the two groups in the serum complement levels, MBL levels, B-cell subsets and other T lymphocyte subsets.
Conclusion
Subjects with CPA secondary to PTLA have impaired neutrophil oxidative burst and a lower Th-1 response than controls.
Open Research
DATA AVAILABILITY STATEMENT
The data will be made available on a reasonable request to the corresponding author.
REFERENCES
- 1Denning DW, Cole DC, Ray A. New estimation of the prevalence of chronic pulmonary aspergillosis (CPA) related to pulmonary TB—a revised burden for India. IJID Reg. 2023; 6: 7-14.
- 2Sehgal IS, Choudhary H, Dhooria S, et al. Diagnostic cut-off of aspergillus fumigatus-specific IgG in the diagnosis of chronic pulmonary aspergillosis. Mycoses. 2018; 61(10): 770-776.
- 3Denning DW, Pleuvry A, Cole DC. Global burden of chronic pulmonary aspergillosis as a sequel to pulmonary tuberculosis. Bull World Health Organ. 2011; 89(12): 864-872.
- 4Sehgal IS, Dhooria S, Sachdeva N, et al. Role of serum procalcitonin in the diagnosis and monitoring of treatment response in treatment-naïve subjects with chronic pulmonary aspergillosis. Heliyon. 2023; 9(4):e15356.
- 5Sehgal IS, Dhooria S, Muthu V, et al. Identification of distinct immunophenotypes in chronic pulmonary aspergillosis using cluster analysis. Mycoses. 2023; 66(4): 299-303.
- 6Sehgal IS, Dhooria S, Muthu V, et al. Efficacy of 12-months oral itraconazole versus 6-months oral itraconazole to prevent relapses of chronic pulmonary aspergillosis: an open-label, randomised controlled trial in India. Lancet Infect Dis. 2022; 22(7): 1052-1061.
- 7Page ID, Byanyima R, Hosmane S, et al. Chronic pulmonary aspergillosis commonly complicates treated pulmonary tuberculosis with residual cavitation. Eur Respir J. 2019; 53(3): 1801184.
- 8Aspergilloma and residual tuberculous cavities—the results of a resurvey. Tubercle. 1970; 51(3): 227-245.
- 9Aspergillus in persistent lung cavities after tuberculosis. A report from the research committee of the British tuberculosis association. Tubercle. 1968; 49(1): 1-11.
- 10Smith NL, Hankinson J, Simpson A, Bowyer P, Denning DW. A prominent role for the IL1 pathway and IL15 in susceptibility to chronic cavitary pulmonary aspergillosis. Clin Microbiol Infect. 2014; 20(8): O480-O488.
- 11Smith NL, Bromley MJ, Denning DW, Simpson A, Bowyer P. Elevated levels of the neutrophil chemoattractant pro-platelet basic protein in macrophages from individuals with chronic and allergic aspergillosis. J Infect Dis. 2015; 211(4): 651-660.
- 12Denning DW, Riniotis K, Dobrashian R, Sambatakou H. Chronic cavitary and fibrosing pulmonary and pleural aspergillosis: case series, proposed nomenclature change, and review. Clin Infect Dis. 2003; 37(Suppl 3): S265-S280.
- 13Sambatakou H, Pravica V, Hutchinson IV, Denning DW. Cytokine profiling of pulmonary aspergillosis. Int J Immunogenet. 2006; 33(4): 297-302.
- 14von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007; 370(9596): 1453-1457.
- 15Sehgal IS, Dhooria S, Choudhary H, et al. Efficiency of a fumigatus-specific IgG and galactomannan testing in the diagnosis of simple aspergilloma. Mycoses. 2019; 62(12): 1108-1115.
- 16Sehgal IS, Dhooria S, Choudhary H, et al. Utility of serum and Bronchoalveolar lavage fluid galactomannan in diagnosis of chronic pulmonary Aspergillosis. J Clin Microbiol. 2019; 57(3): e01821-18.
- 17Denning DW, Cadranel J, Beigelman-Aubry C, et al. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. Eur Respir J. 2016; 47(1): 45-68.
- 18Sehgal IS, Dhooria S, Muthu V, Prasad KT, Agarwal R. An overview of the available treatments for chronic cavitary pulmonary aspergillosis. Expert Rev Respir Med. 2020; 14(7): 715-727.
- 19Pilania RK, Rawat A, Shandilya J, et al. Pediatric systemic lupus erythematosus: phagocytic defect and oxidase activity of neutrophils. Pediatr Res. 2022; 92(6): 1535-1542.
- 20Bongomin F, Harris C, Foden P, Kosmidis C, Denning DW. Innate and adaptive immune defects in chronic pulmonary Aspergillosis. J Fungi (Basel). 2017; 3(2):26.
- 21Carvalho A, Pasqualotto AC, Pitzurra L, Romani L, Denning DW, Rodrigues F. Polymorphisms in toll-like receptor genes and susceptibility to pulmonary aspergillosis. J Infect Dis. 2008; 197(4): 618-621.
- 22Smith NL, Hankinson J, Simpson A, Denning DW, Bowyer P. Reduced expression of TLR3, TLR10 and TREM1 by human macrophages in chronic cavitary pulmonary aspergillosis, and novel associations of VEGFA, DENND1B and PLAT. Clin Microbiol Infect. 2014; 20(11): O960-O968.
- 23Vaid M, Kaur S, Sambatakou H, Madan T, Denning DW, Sarma PU. Distinct alleles of mannose-binding lectin (MBL) and surfactant proteins a (SP-A) in patients with chronic cavitary pulmonary aspergillosis and allergic bronchopulmonary aspergillosis. Clin Chem Lab Med. 2007; 45(2): 183-186.
- 24Crosdale DJ, Poulton KV, Ollier WE, Thomson W, Denning DW. Mannose-binding lectin gene polymorphisms as a susceptibility factor for chronic necrotizing pulmonary aspergillosis. J Infect Dis. 2001; 184(5): 653-656.
- 25Harrison E, Singh A, Morris J, et al. Mannose-binding lectin genotype and serum levels in patients with chronic and allergic pulmonary aspergillosis. Int J Immunogenet. 2012; 39(3): 224-232.
- 26Colombo SAP, Hashad R, Denning DW, et al. Defective interferon-gamma production is common in chronic pulmonary Aspergillosis. J Infect Dis. 2022; 225(10): 1822-1831.
- 27Rodland EK, Ueland T, Bjornsen S, et al. Systemic biomarkers of inflammation and haemostasis in patients with chronic necrotizing pulmonary aspergillosis. BMC Infect Dis. 2012; 12:144.
- 28Kosmidis C, Powell G, Borrow R, Morris J, Alachkar H, Denning DW. Response to pneumococcal polysaccharide vaccination in patients with chronic and allergic aspergillosis. Vaccine. 2015; 33(51): 7271-7275.
- 29Pandit H, Madhukaran SP, Nayak A, Madan T. SP-A and SP-D in host defense against fungal infections and allergies. Front Biosci (Elite Ed). 2012; 4: 651-661.
- 30He Q, Li H, Rui Y, et al. Pentraxin 3 gene polymorphisms and pulmonary Aspergillosis in chronic obstructive pulmonary disease patients. Clin Infect Dis. 2018; 66(2): 261-267.
- 31Ren W, Li H, Guo C, et al. Serum cytokine biomarkers for use in diagnosing pulmonary tuberculosis versus chronic pulmonary Aspergillosis. Infect Drug Resist. 2023; 16: 2217-2226.
- 32Zhang H, Costabel U, Dai H. The role of diverse immune cells in sarcoidosis. Front Immunol. 2021; 12:788502.
- 33Agarwal R. Allergic bronchopulmonary aspergillosis: lessons learnt from genetics. Indian J Chest Dis Allied Sci. 2011; 53(3): 137-140.
- 34Agarwal R, Chakrabarti A, Shah A, et al. Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria. Clin Exp Allergy. 2013; 43(8): 850-873.
- 35Agarwal R, Sehgal IS, Dhooria S, Aggarwal AN. Developments in the diagnosis and treatment of allergic bronchopulmonary aspergillosis. Expert Rev Respir Med. 2016; 10(12): 1317-1334.
- 36Gazendam RP, van Hamme JL, Tool AT, et al. Human neutrophils use different mechanisms to kill aspergillus fumigatus conidia and hyphae: evidence from phagocyte defects. J Immunol. 2016; 196(3): 1272-1283.
- 37Kauffman HF, van der Heide S, Beaumont F, Blok H, de Vries K. Class-specific antibody determination against aspergillus fumigatus by means of the enzyme-linked immunosorbent assay. III. Comparative study: IgG, IgA, IgM ELISA titers, precipitating antibodies and IgE binding after fractionation of the antigen. Int Arch Allergy Appl Immunol. 1986; 80(3): 300-306.
- 38Kurup VP, Resnick A, Kalbfleish J, Fink JN. Antibody isotype responses in aspergillus-induced diseases. J Lab Clin Med. 1990; 115(3): 298-303.
- 39Kelleher P, Goodsall A, Mulgirigama A, et al. Interferon-gamma therapy in two patients with progressive chronic pulmonary aspergillosis. Eur Respir J. 2006; 27(6): 1307-1310.
- 40Monk EJM, Harris C, Doffinger R, Hayes G, Denning DW, Kosmidis C. Interferon gamma replacement as salvage therapy in chronic pulmonary aspergillosis: effects on frequency of acute exacerbation and all-cause hospital admission. Thorax. 2020; 75(6): 513-516.
- 41Döffinger R, Harris C, Lear S, Newton P, Alachkar H, Dinakantha S. Impaired Th1 and Th17 immunity in chronic pulmonary aspergillosis. NHS England National Commissiong Group Chronic Pulmonary Aspergillosis National Service, The National Aspergillosis Centre Annual Report. 2013;2014:202013-4.
- 42Jolink H, de Boer R, Hombrink P, et al. Pulmonary immune responses against aspergillus fumigatus are characterized by high frequencies of IL-17 producing T-cells. J Infect. 2017; 74(1): 81-88.
- 43Chai LY, van de Veerdonk F, Marijnissen RJ, et al. Anti-aspergillus human host defence relies on type 1 T helper (Th1), rather than type 17 T helper (Th17), cellular immunity. Immunology. 2010; 130(1): 46-54.
- 44LeibundGut-Landmann S. Tissue-resident memory T cells in antifungal immunity. Front Immunol. 2021; 12:693055.
- 45Omilusik KD, Goldrath AW. The origins of memory T cells. Nature. 2017; 552(7685): 337-339.
- 46Saint-André V, Charbit B, Biton A, et al. Smoking changes adaptive immunity with persistent effects. Nature. 2024; 626(8000): 827-835.
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