The role of immune homeostasis in patients with new coronavirus infection (COVID-19) in the development of invasive pulmonary aspergillosis

Abstract

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.

Keywords

• indolamine-2,3-dioxygenase
• aryl hydrocarbon receptor
• kynurenine
• inflammation
• tolerance
• covid-19
• invasive pulmonary aspergillosis