jofinЖурнал инфектологииJournal Infectology2072-6732IPO “АIDSSPbR"10.22625/2072-6732-2023-15-2-14-23jofin-1500Research ArticleОбзорReviewРоль иммунного гомеостаза у пациентов с новой коронавирусной инфекцией (COVID-19) в развитии инвазивного аспергиллеза легкихThe role of immune homeostasis in patients with new coronavirus infection (COVID-19) in the development of invasive pulmonary aspergillosisТараскинаА. Е.TaraskinaA. E.

Тараскина Анастасия Евгеньевна – заведующая НИЛ молекулярно-генетической микробиологии, к.б.н., тел.: 8(812)303-51-46

Санкт-Петербург

Saint-Petersburg

anastasiya.taraskina@szgmu.ruФроловаЕ. В.FrolovaE. V.

Фролова Екатерина Васильевна – заведующая НИЛ иммунологии и аллергологии, к.м.н.; тел.: 8(812)303-51-46

Санкт-Петербург

Saint-Petersburg

ekaterina.frolova@szgmu.ruШадривоваО. В.ShadrivovaO. V.

Шадривова Ольга Витальевна – доцент кафедры клинической микологии, аллергологии и иммунологии, к.м.н.; тел.: 8(812)303-51-46

Санкт-Петербург

Saint-Petersburg

olshadr@mail.ruСекретареваО. В.SekretarevaO. V.

Секретарева Ольга Владимировна – лаборант-исследователь НИЛ иммунологии и аллергологии; тел.: 8(812)303-51-46

Санкт-Петербург

Saint-Petersburg

olga.sekretareva@szgmu.ruВасильеваН. В.VasilyevaN. V.

Васильева Наталья Всеволодовна – директор Научно-исследовательского института медицинской микологии им. П.Н. Кашкина, д.б.н., профессор, заслуженный деятель науки РФ; тел.: 8(812)303-51-40

Санкт-Петербург

Saint-Petersburg

Natalya.Vasileva@szgmu.ruСеверо-Западный государственный медицинский университет им. И.И. МечниковаРоссияNorth-Western State Medical University named after I.I. MechnikovRussian Federation2023060720231521423Copyright © Тараскина А.Е., Фролова Е.В., Шадривова О.В., Секретарева О.В., Васильева Н.В., 20232023Тараскина А.Е., Фролова Е.В., Шадривова О.В., Секретарева О.В., Васильева Н.В.Taraskina A.E., Frolova E.V., Shadrivova O.V., Sekretareva O.V., Vasilyeva N.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.niidi.ru/jofin/article/view/1500

В последнее время все больше внимания уделяется роли индоламин-2,3-диоксигеназы и арилуглеводородного рецептора в поддержании баланса между иммунной реактивностью и толерантностью при различных инфекционных заболеваниях. Известно, что отличительной чертой COVID-19 является активация иммуновоспалительных путей, которые индуцируют индоламин-2,3-диоксигеназу – ключевой фермент, катализирующий метаболизм триптофана по кинурениновому пути, тем самым изменяя соотношение кинуренина/триптофана в сыворотке крови больных. Важным свойством SARS-CoV-2 является его способность связываться с арилуглеводородным рецептором, что приводит к увеличению внутриклеточной экспрессии индоламин-2,3-диоксигеназы и продукции кинуренина на начальной стадии инфекции. Длительная активация арилуглеводородного рецептора повышает выработку интерлейкина-6, усиливая воспалительное состояние и противодействуя иммунной толерантности на более поздних стадиях COVID-19. В совокупности эти данные указывают на важную роль индоламин-2,3-диоксигеназы и арилуглеводородного рецептора в контролировании воспаления у пациентов с COVID-19. Нарушение регуляции иммунного ответа не только ставит под угрозу способность хозяина справиться с SARS-CoV-2, но также может предрасполагать человека к вторичным бактериальным и грибковым инфекциям. Среди вторичных инфекций, которые возникают у пациентов с новой коронавирусной инфекцией, COVID-19-ассоциированный инвазивный аспергиллез легких является важной причиной смертности, хотя многие аспекты болезни все еще остаются нерешенными. В данном обзоре представлены современные представления о значении метаболитов триптофана и иммунологических факторов в патогенезе COVID-19 и инвазивного аспергиллеза легких.

Recently, more attention has been paid to the role of indolamine-2,3-dioxygenase and aryl hydrocarbon receptor in maintaining a balance between immune reactivity and tolerance in various infectious diseases. It is known that the hallmark of COVID-19 is the activation of immuno-inflammatory pathways that induce indoleamine-2,3-dioxygenase, a key enzyme that catalyzes the metabolism of tryptophan along the kynurenine pathway, thereby changing the ratio of kynurenine/tryptophan in the blood serum of patients. An important property of SARS-CoV-2 is its ability to bind to aryl hydrocarbon receptor, which leads to an increase in intracellular expression of indolamine-2,3-dioxygenase and production of kynurenine at the initial stage of infection. Long-term activation of the aryl hydrocarbon receptor increases the production of interleukin-6, enhancing the inflammatory state and counteracting immune tolerance in the later stages of COVID-19. In aggregate, these data point to an important role of indolamine 2,3-dioxygenase and the aryl hydrocarbon receptor in controlling inflammation in patients with COVID-19. Dysregulation of the immune response not only threaten the host’s ability to cope with SARS-CoV-2, but can also predispose a person to secondary bacterial and fungal infections. Among the secondary infections that occur in patients with new coronavirus infection, COVID-19-associated invasive pulmonary aspergillosis is an important cause of death, although many aspects of the disease still remain unresolved. This review presents the current understanding of the importance of tryptophan metabolites and immunological factors in the pathogenesis of COVID-19 and invasive pulmonary aspergillosis.

индоламин-23-диоксигеназаарилуглеводородный рецепторкинуренинвоспалениетолерантностьCOVID-19инвазивный аспергиллез легкихindolamine-23-dioxygenasearyl hydrocarbon receptorkynurenineinflammationtoleranceCOVID-19invasive pulmonary aspergillosisReferencesZelante T, Iannitti RG, Fallarino F, et al. Tryptophan feeding of the IDO1-AhR axis in host-microbial symbiosis. Front Immunol. 2014 Dec 15;5:640.Zelante T, Iannitti RG, Fallarino F, et al. Tryptophan feeding of the IDO1-AhR axis in host-microbial symbiosis. Front Immunol. 2014 Dec 15;5:640.Булгакова, С.В. Иммунный гомеостаз. Новая роль микро- и макроэлементов, здоровый микробиоты / С.В. Булгакова, Н.П. Романчук // Бюллетень науки и практики. – 2020. – Т. 6, № 10. – С. 206–233.Bulgakova S.V., Romanchuk N.P. // Bjulleten’ nauki i praktiki. – 2020. – T. 6, № 10. – S. 206–233.Badawy AA. Kynurenine Pathway of Tryptophan Metabolism: Regulatory and Functional Aspects. Int J Tryptophan Res. 2017 Mar 15; 10:1178646917691938Badawy AA. Kynurenine Pathway of Tryptophan Metabolism: Regulatory and Functional Aspects. Int J Tryptophan Res. 2017 Mar 15; 10:1178646917691938Engin AB, Engin ED, Engin A. The effect of environmental pollution on immune evasion checkpoint of SARS-CoV-2. Environmental toxicology and pharmacology. 2021 Jan; 81: 103520.Engin AB, Engin ED, Engin A. The effect of environmental pollution on immune evasion checkpoint of SARS-CoV-2. Environmental toxicology and pharmacology. 2021 Jan; 81: 103520.Anderson G, Carbone A, Mazzoccoli G. Tryptophan Metabolites and Aryl Hydrocarbon Receptor in Severe Acute Respiratory Syndrome, Coronavirus-2 (SARS-CoV-2) Pathophysiology. Int J Mol Sci. 2021 Feb 5; 22(4):1597.Anderson G, Carbone A, Mazzoccoli G. Tryptophan Metabolites and Aryl Hydrocarbon Receptor in Severe Acute Respiratory Syndrome, Coronavirus-2 (SARS-CoV-2) Pathophysiology. Int J Mol Sci. 2021 Feb 5; 22(4):1597.Guarnieri T. Hypothesis: Emerging Roles for Aryl Hydrocarbon Receptor in rchestrating CoV-2-Related Inflammation. Cells. 2022 Feb 13; 11(4):648.Guarnieri T. Hypothesis: Emerging Roles for Aryl Hydrocarbon Receptor in rchestrating CoV-2-Related Inflammation. Cells. 2022 Feb 13; 11(4):648.Almulla AF, Supasitthumrong T, Tunvirachaisakul C, et al. The tryptophan catabolite or kynurenine pathway in COVID-19 and critical COVID-19: a systematic review and metaanalysis. BMC Infect Dis. 2022 Jul 15; 22(1):615.Almulla AF, Supasitthumrong T, Tunvirachaisakul C, et al. The tryptophan catabolite or kynurenine pathway in COVID-19 and critical COVID-19: a systematic review and meta-analysis. BMC Infect Dis. 2022 Jul 15; 22(1):615.Климко, Н.Н. Распространенность тяжелых и хронических микотических заболеваний в российской федерации по модели life program / Н.Н. Климко, Я.И. Козлова, С.Н. Хостелиди, О.В. Шадривова // Проблемы медицинской микологии. – 2014. – Т. 16, № 1. – С. 3–8.Klimko N.N., Kozlova Ja.I., Hostelidi S.N., Shadrivova O.V. // Problemy medicinskoj mikologii. – 2014. – T. 16, № 1. – S. 3–8. Klimko N.N., Kozlova Ja.I., Hostelidi S.N., Shadrivova O.V. // Problemy medicinskoj mikologii. – 2014. – T. 16, № 1. – S. 3–8.Cadena J, Thompson GR 3rd, Patterson TF. Aspergillosis: Epidemiology, Diagnosis, and Treatment. Infect Dis Clin North Am. 2021 Jun; 35(2):415-434.Cadena J, Thompson GR 3rd, Patterson TF. Aspergillosis: Epidemiology, Diagnosis, and Treatment. Infect Dis Clin North Am. 2021 Jun; 35(2):415-434.Шадривова, О.В. Молекулярно-генетические и иммунологические аспекты инвазивного аспергиллеза / О.В. Шадривова, Е.В. Фролова, А.Е. Тараскина, Н.Н. Климко // Журнал инфектологии. – 2017. – Т. 9, № 1. – С. 47–54.Shadrivova O.V., Frolova E.V., Taraskina A.E., Klimko N.N. // Zhurnal infektologii. – 2017. – T. 9, № 1. – S. 47–54.Gu X, Hua YH, Zhang YD, et al. The Pathogenesis of Aspergillus fumigatus, Host Defense Mechanisms, and the Development of AFMP4 Antigen as a Vaccine. Pol J Microbiol. 2021 Mar; 70(1):3-11.Gu X, Hua YH, Zhang YD, et al. The Pathogenesis of Aspergillus fumigatus, Host Defense Mechanisms, and the Development of AFMP4 Antigen as a Vaccine. Pol J Microbiol. 2021 Mar; 70(1):3-11.Musuuza JS, Watson L, Parmasad V, et al. Prevalence and outcomes of co-infection and superinfection with SARS-CoV-2 and other pathogens: A systematic review and meta-analysis. PLoS One. 2021 May 6; 16(5):e0251170.Musuuza JS, Watson L, Parmasad V, et al. Prevalence and outcomes of co-infection and superinfection with SARS-CoV-2 and other pathogens: A systematic review and meta-analysis. PLoS One. 2021 May 6; 16(5):e0251170.Garcia-Vidal C, Sanjuan G, Moreno-García E, et al. COVID-19 Researchers Group. Incidence of co-infections and super-infections in hospitalized patients with COVID-19: a retrospective cohort study. Clin Microbiol Infect. 2021 Jan; 27(1):83-88.Garcia-Vidal C, Sanjuan G, Moreno-García E, et al. COVID-19 Researchers Group. Incidence of co-infections and superinfections in hospitalized patients with COVID-19: a retrospective cohort study. Clin Microbiol Infect. 2021 Jan; 27(1):83-88.Abdoli A, Falahi S, Kenarkoohi A. COVID-19-associated opportunistic infections: a snapshot on the current reports. Clin Exp Med. 2022 Aug; 22(3):327-346.Abdoli A, Falahi S, Kenarkoohi A. COVID-19-associated opportunistic infections: a snapshot on the current reports. Clin Exp Med. 2022 Aug; 22(3):327-346.Shadrivova O, Gusev D, Vashukova M, Lobzin D, et al. COVID-19-Associated Pulmonary Aspergillosis in Russia. J Fungi (Basel). 2021 Dec 10; 7(12):1059.Shadrivova O, Gusev D, Vashukova M, Lobzin D, et al. COVID-19-Associated Pulmonary Aspergillosis in Russia. J Fungi (Basel). 2021 Dec 10; 7(12):1059.Климко, Н.Н. Инвазивный аспергиллёз при тяжёлых респираторных вирусных инфекциях (гриппе и COVID-19) / Н.Н. Климко, О.В. Шадривова // Журнал инфектологии. – 2021. – Т.13, № 4. – С. 14–24.Klimko N.N., Shadrivova O.V. // Zhurnal infektologii. – 2021. – T.13, №4. – S.14–24.Dellière S, Dudoignon E, Fodil S, et al. Risk factors associated with COVID-19-associated pulmonary aspergillosis in ICU patients: a French multicentric retrospective cohort. Clin Microbiol Infect. 2020 Dec 13; 27(5):790.e1–5.Dellière S, Dudoignon E, Fodil S, et al. Risk factors associated with COVID-19-associated pulmonary aspergillosis in ICU patients: a French multicentric retrospective cohort. Clin Microbiol Infect. 2020 Dec 13; 27(5):790.e1–5.Mándi, Y.; Vécsei, L. The kynurenine system and immunoregulation. J Neural Transm (Vienna). 2012 Feb; 119(2):197-209.Mándi, Y.; Vécsei, L. The kynurenine system and immunoregulation. J Neural Transm (Vienna). 2012 Feb; 119(2):197-209.Murakami Y, Hoshi M, Imamura Y, et al. Remarkable role of indoleamine 2,3-dioxygenase and tryptophan metabolites in infectious diseases: potential role in macrophage-mediated inflammatory diseases. Mediators Inflamm. 2013; 2013:391984.Murakami Y, Hoshi M, Imamura Y, et al. Remarkable role of indoleamine 2,3-dioxygenase and tryptophan metabolites in infectious diseases: potential role in macrophage-mediated inflammatory diseases. Mediators Inflamm. 2013; 2013:391984.Zhou L. Ahr function in lymphocytes: emerging concepts. Trends Immunol. 2016 Jan; 37(1):17-31.Zhou L. Ahr function in lymphocytes: emerging concepts. Trends Immunol. 2016 Jan; 37(1):17-31.Pallotta MT, Fallarino F, Matino D, et al. AhR-mediated, non-genomic of IDO1 function. Front Immunol. 2014 Oct 15; 5:497.Pallotta MT, Fallarino F, Matino D, et al. AhR-mediated, non-genomic of IDO1 function. Front Immunol. 2014 Oct 15; 5:497.Jaronen M, Quintana FJ. Immunological relevance of the coevolution of IDO1 and AhR. Front Immunol. 2014 Oct 20; 5:521.Jaronen M, Quintana FJ. Immunological relevance of the coevolution of IDO1 and AhR. Front Immunol. 2014 Oct 20; 5:521.Guarnieri T; Abruzzo PM, Bolotta A. More than a cell biosensor: Aryl hydrocarbon receptor at the intersection of physiology and inflammation. Am J Physiol Cell Physiol. 2020 Jun 1; 318(6):C1078-C1082.Guarnieri T; Abruzzo PM, Bolotta A. More than a cell biosensor: Aryl hydrocarbon receptor at the intersection of physiology and inflammation. Am J Physiol Cell Physiol. 2020 Jun 1; 318(6):C1078-C1082.Guan WJ, Ni ZY, Hu Y, Liang WH, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30; 382(18):1708-1720.Guan WJ, Ni ZY, Hu Y, Liang WH, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30; 382(18):1708-1720.Глазанова, Т.В. Нарушения в системе иммунитета после перенесенной новой коронавирусной инфекции COVID-19 / Т.В. Глазанова, Е.Р. Шилова // Журнал инфектологии. – 2022. – Т.14, № 4. – С.26–37.Glazanova T.V., Shilova E.R. // Zhurnal infektologii. – 2022. – T.14, №4. – S.26–37.Costantini C, van de Veerdonk FL, Romani L. Covid-19-Associated Pulmonary Aspergillosis: The Other Side of the Coin. Vaccines (Basel). 2020 Dec 1; 8(4):713.Costantini C, van de Veerdonk FL, Romani L. Covid-19-Associated Pulmonary Aspergillosis: The Other Side of the Coin. Vaccines (Basel). 2020 Dec 1; 8(4):713.Salazar F, Bignell E, Brown GD, et al. Pathogenesis of Respiratory Viral and Fungal Coinfections. Clin Microbiol Rev. 2022 Jan 19; 35(1):e0009421.Salazar F, Bignell E, Brown GD, et al. Pathogenesis of Respiratory Viral and Fungal Coinfections. Clin Microbiol Rev. 2022 Jan 19; 35(1):e0009421.Salmanton-García J, Sprute R, Stemler J et al. COVID-19-associated pulmonary aspergillosis, march-august 2020. Emerg Infect Dis. 2021; 27(4):1077–1086.Salmanton-García J, Sprute R, Stemler J et al. COVID-19-associated pulmonary aspergillosis, march-august 2020. Emerg Infect Dis. 2021; 27(4):1077–1086.Er B, Er AG, Gülmez D et al. A screening study for COVID-19-associated pulmonary aspergillosis in critically ill patients during the third wave of the pandemic. Mycoses. 2022 Jul; 65(7):724-732.Er B, Er AG, Gülmez D et al. A screening study for COVID-19-associated pulmonary aspergillosis in critically ill patients during the third wave of the pandemic. Mycoses. 2022 Jul; 65(7):724-732.Chong WH, Saha BK, Neu KP. Comparing the clinical characteristics and outcomes of COVID-19-associate pulmonary aspergillosis (CAPA): a systematic review and meta-analysis. Infection. 2022 Feb; 50(1):43-56.Chong WH, Saha BK, Neu KP. Comparing the clinical characteristics and outcomes of COVID-19-associate pulmonary aspergillosis (CAPA): a systematic review and meta-analysis. Infection. 2022 Feb; 50(1):43-56.Prattes J, Wauters J, Giacobbe DR et al. ECMM-CAPA Study Group. Risk factors and outcome of pulmonary aspergillosis in critically ill coronavirus disease 2019 patients-a multinational observational study by the European Confederation of Medical Mycology. Clin Microbiol Infect. 2022 Apr; 28(4):580-587.Prattes J, Wauters J, Giacobbe DR et al. ECMM-CAPA Study Group. Risk factors and outcome of pulmonary aspergillosis in critically ill coronavirus disease 2019 patients-a multinational observational study by the European Confederation of Medical Mycology. Clin Microbiol Infect. 2022 Apr; 28(4):580-587.Blanco-Melo D, Nilsson-Payant BE, Liu W-C, et al. Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19. Cell. 2020 May 28; 181(5):1036-1045.e9.Blanco-Melo D, Nilsson-Payant BE, Liu W-C, et al. Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19. Cell. 2020 May 28; 181(5):1036-1045.e9.Pum A, Ennemoser M, Adage T, Kungl AJ. Cytokines and Chemokines in SARS-CoV-2 Infections—Therapeutic Strategies Targeting Cytokine Storm. Biomolecules. 2021 Jan 12; 11(1):91.Pum A, Ennemoser M, Adage T, Kungl AJ. Cytokines and Chemokines in SARS-CoV-2 Infections—Therapeutic Strategies Targeting Cytokine Storm. Biomolecules. 2021 Jan 12; 11(1):91.Russo A, Morrone HL, Rotundo S, et al. Cytokine Profile of Invasive Pulmonary Aspergillosis in Severe COVID-19 and Possible Therapeutic Targets. Diagnostics (Basel). 2022 Jun 1; 12(6):1364.Russo A, Morrone HL, Rotundo S, et al. Cytokine Profile of Invasive Pulmonary Aspergillosis in Severe COVID-19 and Possible Therapeutic Targets. Diagnostics (Basel). 2022 Jun 1; 12(6):1364.Grunewald ME, Shaban MG, Mackin SR, et al. Murine coronavirus infection activates the aryl hydrocarbon receptor in an indoleamine 2,3-dioxygenase-independent manner, contributing to cytokine modulation and proviral TCDD-inducible-PARP expression. J of Virology. 2020; 94(3): e01743-19.Grunewald ME, Shaban MG, Mackin SR, et al. Murine coronavirus infection activates the aryl hydrocarbon receptor in an indoleamine 2,3-dioxygenase-independent manner, contributing to cytokine modulation and proviral TCDD-inducible-PARP expression. J of Virology. 2020; 94(3): e01743-19.Hollingshead BD, Beischlag TV, Dinatale BC, et al. Inflammatory Signaling and Aryl Hydrocarbon Receptor Mediate Synergistic Induction of Interleukin 6 in MCF-7 Cells. Cancer Res. 2008 May 15; 68(10):3609-17.Hollingshead BD, Beischlag TV, Dinatale BC, et al. Inflammatory Signaling and Aryl Hydrocarbon Receptor Mediate Synergistic Induction of Interleukin 6 in MCF-7 Cells. Cancer Res. 2008 May 15; 68(10):3609-17.Orabona C, Pallotta MT, Volpi C, et al. SOCS3 drives proteasomal degradation of indoleamine 2,3-dioxygenase (IDO) and antagonizes IDO-dependent tolerogenesis. Proc Natl Acad Sci USA. 2008 Dec 30; 105(52):20828-33.Orabona C, Pallotta MT, Volpi C, et al. SOCS3 drives proteasomal degradation of indoleamine 2,3-dioxygenase (IDO) and antagonizes IDO-dependent tolerogenesis. Proc Natl Acad Sci USA. 2008 Dec 30; 105(52):20828-33.Kerkvliet N, Shepherd DM, Baecher-Steppan L. T Lymphocytes Are Direct, Aryl Hydrocarbon Receptor (AhR)-Dependent Targets of 2,3,7,8-Tetrachlorodibenzo-pdioxin (TCDD): AhR Expression in Both CD4+ and CD8+ T Cells Is Necessary for Full Suppression of a Cytotoxic T Lymphocyte Response by TCDD. Toxicol Appl Pharmacol. 2002 Dec 1; 185(2):146-52.Kerkvliet N, Shepherd DM, Baecher-Steppan L. T Lymphocytes Are Direct, Aryl Hydrocarbon Receptor (AhR)-Dependent Targets of 2,3,7,8-Tetrachlorodibenzo-pdioxin (TCDD): AhR Expression in Both CD4+ and CD8+ T Cells Is Necessary for Full Suppression of a Cytotoxic T Lymphocyte Response by TCDD. Toxicol Appl Pharmacol. 2002 Dec 1; 185(2):146-52.Wang H, Wang Z, Cao W, et al. Regulatory T cells in COVID-19. Aging Dis. 2021 Oct 1; 12(7):1545-1553.Wang H, Wang Z, Cao W, et al. Regulatory T cells in COVID-19. Aging Dis. 2021 Oct 1; 12(7):1545-1553.Chen, G., Wu, D., Guo, W., et al. Clinical and immunological features of severe and moderate coronavirus disease disease 2019. Jan; 130: 2620–2629.Chen, G., Wu, D., Guo, W., et al. Clinical and immunological features of severe and moderate coronavirus disease disease 2019.Jan; 130: 2620–2629.Jesenak M, Brndiarova M, Urbancikova I, et al. Immune parameters and COVID-19 infection-associations with clinical severity and disease prognosis. Front Cell Infect Microbiol. 2020 Jun 30;10:364.Jesenak M, Brndiarova M, Urbancikova I, et al. Immune parameters and COVID-19 infection-associations with clinical severity and disease prognosis. Front Cell Infect Microbiol. 2020 Jun 30;10:364.Sadeghi A, Tahmasebi S, Mahmood A, et al. Th17 and Treg cells function in SARS-CoV2 patients compared with healthy controls. J Cell Physiol. 2021 Apr; 236(4):2829-2839.Sadeghi A, Tahmasebi S, Mahmood A, et al. Th17 and Treg cells function in SARS-CoV2 patients compared with healthy controls. J Cell Physiol. 2021 Apr; 236(4):2829-2839.Choera T, Zelante T, Romani L, Keller NP. A Multifaceted Role of Tryptophan Metabolism and Indoleamine 2,3-Dioxygenase Activity in Aspergillus fumigatus-Host Interactions. Front Immunol. 2018 Jan 22; 8:1996.Choera T, Zelante T, Romani L, Keller NP. A Multifaceted Role of Tryptophan Metabolism and Indoleamine 2,3-Dioxygenase Activity in Aspergillus fumigatus-Host Interactions. Front Immunol. 2018 Jan 22; 8:1996.Zelante T, De Luca A, Bonifazi P, et al. IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance. Eur J Immunol. 2007 Oct; 37(10):2695-706.Zelante T, De Luca A, Bonifazi P, et al. IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance. Eur J Immunol. 2007 Oct; 37(10):2695-706.Montagnoli C, Fallarino F, Gaziano R, et al. Immunity and tolerance to Aspergillus involve functionally distinct regulatory T cells and tryptophan catabolism. J Immunol. 2006 Feb 1;176(3):1712-23.Montagnoli C, Fallarino F, Gaziano R, et al. Immunity and tolerance to Aspergillus involve functionally distinct regulatory T cells and tryptophan catabolism. J Immunol. 2006 Feb 1;176(3):1712-23.de Araújo EF, Loures FV, Preite NW, et al. Ligands Modulate the Differentiation of Innate Lymphoid Cells and T Helper Cell Subsets That Control the Severity of a Pulmonary Fungal Infection. Front Immunol. 2021 Apr 16; 12:630938.de Araújo EF, Loures FV, Preite NW, et al. Ligands Modulate the Differentiation of Innate Lymphoid Cells and T Helper Cell Subsets That Control the Severity of a Pulmonary Fungal Infection. Front Immunol. 2021 Apr 16; 12:630938.Romani L, Fallarino F, De Luca A, et al. Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease. Nature. 2008 Jan 10; 451(7175):211-5.Romani L, Fallarino F, De Luca A, et al. Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease. Nature. 2008 Jan 10; 451(7175):211-5.Feys S, Gonçalves 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 Aug; 22:2213-2600.Feys S, Gonçalves 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 Aug; 22:2213-2600.Thomas T, Stefanoni D, Reisz JA, et al., COVID-19 infection results in alterations of the kynurenine pathway and fatty acid metabolism that correlate with IL-6 levels and renal status. medRxiv [Preprint]. 2020 May; 16:2020.05.14.20102491.Thomas T, Stefanoni D, Reisz JA, et al., COVID-19 infection results in alterations of the kynurenine pathway and fatty acid metabolism that correlate with IL-6 levels and renal status. medRxiv [Preprint]. 2020 May; 16:2020.05.14.20102491.Lionetto L, Ulivieri M, Capi M, et al. Increased kynurenine-to-tryptophan ratio in the serum of patients infected with SARS-CoV2: An observational cohort study. Biochim Biophys Acta Mol Basis Dis. 2021 Mar; 1867(3):166042.Lionetto L, Ulivieri M, Capi M, et al. Increased kynurenine-to-tryptophan ratio in the serum of patients infected with SARS-CoV2: An observational cohort study. Biochim Biophys Acta Mol Basis Dis. 2021 Mar; 1867(3):166042.Michaelis S, Zelzer S, Schnedl WJ, et al. Assessment of tryptophan and kynurenine as prognostic markers in patients with SARS-CoV-2. Clin Chim Acta. 2022 Jan; 525:29-33.Michaelis S, Zelzer S, Schnedl WJ, et al. Assessment of tryptophan and kynurenine as prognostic markers in patients with SARS-CoV-2. Clin Chim Acta. 2022 Jan; 525:29-33.Cihan M, Doğan Ö, Ceran Serdar C, et al. Kynurenine pathway in Coronavirus disease (COVID-19): Potential role in prognosis. J Clin Lab Anal. 2022 Mar; 36(3):e24257.Cihan M, Doğan Ö, Ceran Serdar C, et al. Kynurenine pathway in Coronavirus disease (COVID-19): Potential role in prognosis. J Clin Lab Anal. 2022 Mar; 36(3):e24257.Bizjak DA, Stangl M, Börner N, et al. Kynurenine serves as useful biomarker in acute, Long- and Post-COVID-19 diagnostics. Front Immunol. 2022 Sep; 13:1004545.Bizjak DA, Stangl M, Börner N, et al. Kynurenine serves as useful biomarker in acute, Long- and Post-COVID-19 diagnostics. Front Immunol. 2022 Sep; 13:1004545.

The authors declare that there are no conflicts of interest present.