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Kinetic host defense of the mice infected with Aspergillus Fumigatus

    Huilin Su

    Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China

    ‡Authors contributed equally

    Search for more papers by this author

    ,
    Chunxiao Li

    Key Laboratory of Cell Proliferation & Regulation Biology of Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, China

    Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China

    ‡Authors contributed equally

    Search for more papers by this author

    ,
    Yu Wang

    Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China

    ,
    Yan Li

    Key Laboratory of Cell Proliferation & Regulation Biology of Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, China

    Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China

    ,
    Lin Dong

    Key Laboratory of Cell Proliferation & Regulation Biology of Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, China

    ,
    Li Li

    Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China

    ,
    Junhao Zhu

    Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China

    ,
    QiangQiang Zhang

    Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China

    ,
    Guangwei Liu

    Key Laboratory of Cell Proliferation & Regulation Biology of Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, China

    Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China

    ,
    Jinhua Xu

    Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China

    &
    Min Zhu

    *Author for correspondence:

    E-mail Address: juneminmyco@126.com

    Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China

    Published Online:https://doi.org/10.2217/fmb-2019-0043

    Aim:Aspergillus fumigatus is one of the most common opportunistic fungi that can cause invasive infection. To profile the kinetic variation of immune cells and cytokines after exposure to A. fumigatus thoroughly, we established a pulmonary A. fumigatus infection model in temporarily immunosuppressed mice. Materials & methods: Systematic and kinetic studies of different immune cells and cytokines were performed. Results: We observed that the granulocytes and macrophages recruited to the site of infection played an important role in the infectious phase. There was a significant increase in the cytokines IFN-γ, IL-6, TNF-α as well as the chemokines CXCL1, MIP-1α, MIP-2 and CCL5 after infection. IL-10 was found to participate in balancing the anti-inflammatory response in the recovery phases. The immune response mediated by T cells was mainly presented by the Th1-type on day 7 after exposure with a high proportion of IFN-γ+ CD4+ T cells and CD4+CD44highCD62Llow effector T cells. Conclusion: These kinetic parameters of the immune response might provide diagnostic clues for A. fumigatus infection.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1. Van De Veerdonk FL, Gresnigt MS, Romani L, Netea MG, Latge JP. Aspergillus fumigatus morphology and dynamic host interactions. Nat. Rev. Microbiol. 15(11), 661–674 (2017).
    • 2. Kosmidis C, Denning DW. The clinical spectrum of pulmonary aspergillosis. Thorax 70(3), 270–277 (2015).
    • 3. Ullmann AJ, Aguado JM, Arikan-Akdagli S et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin. Microbiol. Infect. 24(Suppl. 1), e1–e38 (2018).
    • 4. Dragonetti G, Criscuolo M, Fianchi L, Pagano L. Invasive aspergillosis in acute myeloid leukemia: are we making progress in reducing mortality? Med. Mycol. 55(1), 82–86 (2017).
    • 5. Xie L, Gebre W, Szabo K, Lin JH. Cardiac aspergillosis in patients with acquired immunodeficiency syndrome: a case report and review of the literature. Arch. Pathol. Lab. Med. 129, 511–515 (2005).
    • 6. Peghin M, Monforte V, Martin-Gomez MT et al. 10 years of prophylaxis with nebulized liposomal amphotericin B and the changing epidemiology of Aspergillus spp. infection in lung transplantation. Transpl. Int. 29(1), 51–62 (2016).
    • 7. Siddiqui AA, Shah AA, Bashir SH. Craniocerebral aspergillosis of sinonasal origin in immunocompetent patients: clinical spectrum and outcome in 25 cases. Neurosurgery 55(3), 602–611; discussion 611–603 (2004). • More and more aspergillosis cases in immunocompetent patients.
    • 8. Sethi P, Saluja R, Jindal N, Singh V. Invasive aspergillosis in an immunocompetent host. JOMFP 16(2), 297–300 (2012).
    • 9. Kim JH, Lee HL, Kim L et al. Airway centered invasive pulmonary aspergillosis in an immunocompetent patient: case report and literature review. J. Thorac. Dis. 8(3), E250–E254 (2016).
    • 10. Youssef M, Bassim M, Shabb N, Kanj SS. Aspergillus mastoiditis in an immunocompetent patient: a case report and review of the literature. Scand. J. Infect. Dis. 46(4), 325–330 (2014).
    • 11. Mohammed AP, Dhunputh P, Chiluka R, Umakanth S. An unusual case of invasive aspergillosis in an immunocompetent individual. BMJ Case Rep. 2015 , pii:bcr2015210381 (2015).
    • 12. Meersseman W, Vandecasteele SJ, Wilmer A, Verbeken E, Peetermans WE, Van Wijngaerden E. Invasive aspergillosis in critically ill patients without malignancy. Am. J. Respir. Crit. Care Med. 170(6), 621–625 (2004).
    • 13. Guinea J, Torres-Narbona M, Gijon P et al. Pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: incidence, risk factors, and outcome. Clin. Microbiol. Infect. 16(7), 870–877 (2010).
    • 14. Cornillet A, Camus C, Nimubona S et al. Comparison of epidemiological, clinical, and biological features of invasive aspergillosis in neutropenic and nonneutropenic patients: a 6-year survey. Clin. Infect. Dis. 43(5), 577–584 (2006).
    • 15. Desoubeaux G, Cray C. Rodent models of invasive aspergillosis due to Aspergillus fumigatus: still a long path toward standardization. Front. Microbiol. 8, 841 (2017).
    • 16. Desoubeaux G, Cray C. Animal models of aspergillosis. Comp. Med. 68(2), 109–123 (2018).
    • 17. Duong M, Ouellet N, Simard M, Bergeron Y, Olivier M, Bergeron MG. Kinetic study of host defense and inflammatory response to Aspergillus fumigatus in steroid-induced immunosuppressed mice. J. Infect. Dis. 178(5), 1472–1482 (1998).
    • 18. Kidney Disease: Improving Global Outcomes Transplant Work G. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am. J. Transplant. 9(Suppl. 3), S1–S155 (2009).
    • 19. Heemann U, Abramowicz D, Spasovski G, Vanholder R. Endorsement of the Kidney Disease Improving Global Outcomes (KDIGO) guidelines on kidney transplantation: a European Renal Best Practice (ERBP) position statement. Nephrol. Dial. Transplant. 26(7), 2099–2106 (2011).
    • 20. Camargo JF, Husain S. Immune correlates of protection in human invasive aspergillosis. Clin. Infect. Dis. 59(4), 569–577 (2014).
    • 21. Balloy V, Chignard M. The innate immune response to Aspergillus fumigatus. Microbes. Infect. 11(12), 919–927 (2009). • The importance of macrophages and neutrophil in Aspergillus infection.
    • 22. Schleimer RP, Kato A, Kern R, Kuperman D, Avila PC. Epithelium: at the interface of innate and adaptive immune responses. J. Allergy Clin. Immunol. 120(6), 1279–1284 (2007).
    • 23. Lobermann M, Borso D, Hilgendorf I, Fritzsche C, Zettl UK, Reisinger EC. Immunization in the adult immunocompromised host. Autoimmun. Rev. 11(3), 212–218 (2012).
    • 24. Cunha C, Kurzai O, Löffler J, Aversa F, Romani L, Carvalho A. Neutrophil responses to aspergillosis: new roles for old players. Mycopathologia 178(5–6), 387–393 (2014).
    • 25. Urban CF, Nett JE. Neutrophil extracellular traps in fungal infection. Semin. Cell Dev. Biol. doi:10.1016/j.semcdb.2018.03.020 (2018) (Epub ahead of print).
    • 26. Raad II, Chaftari AM, Al Shuaibi MM et al. Granulocyte transfusions in hematologic malignancy patients with invasive pulmonary aspergillosis: outcomes and complications. Ann. Oncol. 24(7), 1873–1879 (2013).
    • 27. Segal BH. Role of macrophages in host defense against aspergillosis and strategies for immune augmentation. Oncologist 12(Suppl. 2), 7–13 (2007).
    • 28. Dewi IMW, Van De Veerdonk FL, Gresnigt MS. The multifaceted role of T-helper responses in host defense against Aspergillus fumigatus. J. Fungi (Basel) 3(4), pii:E55 (2017).
    • 29. Zelante T, De Luca A, D’angelo C, Moretti S, Romani L. IL-17/Th17 in anti-fungal immunity: what’s new? Eur. J. Immunol. 39(3), 645–648 (2009).
    • 30. Thakur R, Anand R, Tiwari S, Singh AP, Tiwary BN, Shankar J. Cytokines induce effector T-helper cells during invasive aspergillosis; what we have learned about T-helper cells? Front. Microbiol. 66, 429 (2015).
    • 31. Cenci E, Mencacci A, Fe D’ostiani C et al. Cytokine- and T helper-dependent lung mucosal immunity in mice with invasive pulmonary aspergillosis. J. Infect. Dis. 178(6), 1750–1760 (1998).
    • 32. Chai 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 130(1), 46–54 (2010). • T-cell immunity mainly relied on Th1 type in Aspergillus infection.
    • 33. Werner JL, Gessner MA, Lilly LM et al. Neutrophils produce interleukin 17A (IL-17A) in a dectin-1- and IL-23-dependent manner during invasive fungal infection. Infect. Immun. 79(10), 3966–3977 (2011).
    • 34. Guerra ES, Lee CK, Specht CA et al. Central role of IL-23 and IL-17 producing eosinophils as immunomodulatory effector cells in acute pulmonary aspergillosis and allergic asthma. PLoS Pathog. 13(1), e1006175 (2017).
    • 35. Malacco N, Rachid MA, Gurgel I et al. Eosinophil-associated innate IL-17 response promotes Aspergillus fumigatus lung pathology. Front. Cell Infect. Microbiol. 8, 453 (2018).
    • 36. Park SJ, Hughes MA, Burdick M, Strieter RM, Mehrad B. Early NK cell-derived IFN-{gamma} is essential to host defense in neutropenic invasive aspergillosis. J. Immunol. 182(7), 4306–4312 (2009).
    • 37. Lass-Florl C, Roilides E, Loffler J, Wilflingseder D, Romani L. Minireview: host defence in invasive aspergillosis. Mycoses 56(4), 403–413 (2013).
    • 38. Stuehler C, Khanna N, Bozza S et al. Cross-protective TH1 immunity against Aspergillus fumigatus and Candida albicans. Blood 117(22), 5881–5891 (2011).
    • 39. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N. Engl. J. Med. 340(6), 448–454 (1999).
    • 40. Kurtz SL, Foreman O, Bosio CM, Anver MR, Elkins KL. Interleukin-6 is essential for primary resistance to Francisella tularensis live vaccine strain infection. Infect. Immun. 81(2), 585–597 (2012).
    • 41. Shen HP, Tang YM, Song H, Xu WQ, Yang SL, Xu XJ. Efficiency of interleukin 6 and interferon gamma in the differentiation of invasive pulmonary aspergillosis and pneumocystis pneumonia in pediatric oncology patients. Int. J. Infect. Dis. 48, 73–77 (2016). • T-cell immunity mainly relied on Th1 type in Aspergillus infection.
    • 42. Ceesay M, Kordasti S, Berry L et al. Cytokine Profile of Patients with Invasive Aspergillosis: Initial Results from the First 100 Patients Recruited into the Aspergillosis Study. Conference paper European Society of Clinical Microbiology and Infectious Diseases 2011, Milan, Italy, doi:10.13140/2.1.2243.8404 (2011). •• The cytokine profile of patients. It could be combined with basic research together to detect significant markers.
    • 43. Chai L, Netea MG, Teerenstra S et al. Early proinflammatory cytokines and C-reactive protein trends as predictors of outcome in invasive aspergillosis. J. Infect. Dis. 202(9), 1454–1462 (2010). • High initial IL-8 and persistently elevated IL-6, IL-8 and C-reactive protein levels after initiation of treatment may be early predictors of adverse outcome in invasive aspergillosis.
    • 44. Goncalves SM, Lagrou K, Rodrigues CS et al. Evaluation of bronchoalveolar lavage fluid cytokines as biomarkers for invasive pulmonary aspergillosis in at-risk patients. Front. Microbiol. 8, 2362 (2017).
    • 45. Broughton SE, Dhagat U, Hercus TR et al. The GM-CSF/IL-3/IL-5 cytokine receptor family: from ligand recognition to initiation of signaling. Immunol. Rev. 250(1), 277–302 (2012).
    • 46. Safdar A, Rodriguez G, Zuniga J, Al Akhrass F, Georgescu G, Pande A. Granulocyte macrophage colony-stimulating factor in 66 patients with myeloid or lymphoid neoplasms and recipients of hematopoietic stem cell transplantation with invasive fungal disease. Acta Haematol. 129(1), 26–34 (2013).
    • 47. Poddighe D, Mathias CB, Freyschmidt EJ et al. Basophils are rapidly mobilized following initial aeroallergen encounter in naive mice and provide a priming source of IL-4 in adaptive immune responses. J. Biol. Regul. Homeost. Agents 28(1), 91–103 (2014).
    • 48. Naidu BV, Krishnadasan B, Byrne K et al. Regulation of chemokine expression by cyclosporine A in alveolar macrophages exposed to hypoxia and reoxygenation. Ann. Thorac. Surg. 74(3), 899–905; discussion 905 (2002).
    • 49. Schramm R, Liu Q, Thorlacius H. Expression and function of MIP-2 are reduced by dexamethasone treatment in vivo. Br. J. Pharmacol. 131(2), 328–334 (2000).
    • 50. Shahan TA, Sorenson WG, Paulauskis JD, Morey R, Lewis DM. Concentration- and time-dependent upregulation and release of the cytokines MIP-2, KC, TNF, and MIP-1alpha in rat alveolar macrophages by fungal spores implicated in airway inflammation. Am. J. Respir. Cell Mol. Biol. 18(3), 435–440 (1998).
    • 51. Park SJ, Mehrad B. Innate immunity to Aspergillus species. Clin. Microbiol. Rev. 22(4), 535–551 (2009).
    • 52. Cortez KJ, Lyman CA, Kottilil S et al. Functional genomics of innate host defense molecules in normal human monocytes in response to Aspergillus fumigatus. Infect. Immun. 74(4), 2353–2365 (2006).
    • 53. Hogaboam CM, Blease K, Schuh JM. Cytokines and chemokines in allergic bronchopulmonary aspergillosis (ABPA) and experimental Aspergillus-induced allergic airway or asthmatic disease. Front. Biosci. 8, e147–e156 (2003).