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The Interplay between Host Immunity and Respiratory Viral Infection in Asthma Exacerbation
Ferdaus Mohd Altaf Hossain,최진영,Erdenebileg Uyangaa,박성옥,어성국 대한면역학회 2019 Immune Network Vol.19 No.5
Asthma is one of the most common and chronic diseases characterized by multidimensional immune responses along with poor prognosis and severity. The heterogeneous nature of asthma may be attributed to a complex interplay between risk factors (either intrinsic or extrinsic) and specific pathogens such as respiratory viruses, and even bacteria. The intrinsic risk factors are highly correlated with asthma exacerbation in host, which may be mediated via genetic polymorphisms, enhanced airway epithelial lysis, apoptosis, and exaggerated viral replication in infected cells, resulting in reduced innate immune response and concomitant reduction of interferon (types I, II, and III) synthesis. The canonical features of allergic asthma include strong Th2-related inflammation, sensitivity to non-steroidal anti-inflammatory drugs (NSAIDs), eosinophilia, enhanced levels of Th2 cytokines, goblet cell hyperplasia, airway hyper-responsiveness, and airway remodeling. However, the NSAID-resistant non-Th2 asthma shows a characteristic neutrophilic influx, Th1/Th17 or even mixed (Th17-Th2) immune response and concurrent cytokine streams. Moreover, inhaled corticosteroid-resistant asthma may be associated with multifactorial innate and adaptive responses. In this review, we will discuss the findings of various in vivo and ex vivo models to establish the critical heterogenic asthmatic etiologies, host-pathogen relationships, humoral and cell-mediated immune responses, and subsequent mechanisms underlying asthma exacerbation triggered by respiratory viral infections.
Hossain Ferdaus Mohd Altaf,박성옥,김효진,어준철,최진영,Tanveer Maryum,Uyangaa Erdenebelig,김관회,어성국 대한면역학회 2021 Immune Network Vol.21 No.4
Asthma exacerbations are a major cause of intractable morbidity, increases in health care costs, and a greater progressive loss of lung function. Asthma exacerbations are most commonly triggered by respiratory viral infections, particularly with human rhinovirus (hRV). Respiratory viral infections are believed to affect the expression of indoleamine 2,3-dioxygenase (IDO), a limiting enzyme in tryptophan catabolism, which is presumed to alter asthmatic airway inflammation. Here, we explored the detailed role of IDO in the progression of asthma exacerbations using a mouse model for asthma exacerbation caused by hRV infection. Our results reveal that IDO is required to prevent neutrophilic inflammation in the course of asthma exacerbation caused by an hRV infection, as corroborated by markedly enhanced Th17- and Th1-type neutrophilia in the airways of IDO-deficient mice. This neutrophilia was closely associated with disrupted expression of tight junctions and enhanced expression of inflammasome-related molecules and mucin-inducing genes. In addition, IDO ablation enhanced allergen-specific Th17- and Th1-biased CD4+ T-cell responses following hRV infection. The role of IDO in attenuating Th17- and Th1-type neutrophilic airway inflammation became more apparent in chronic asthma exacerbations after repeated allergen exposures and hRV infections. Furthermore, IDO enzymatic induction in leukocytes derived from the hematopoietic stem cell (HSC) lineage appeared to play a dominant role in attenuating Th17- and Th1-type neutrophilic inflammation in the airway following hRV infection. Therefore, IDO activity in HSC-derived leukocytes is required to regulate Th17- and Th1-type neutrophilic inflammation in the airway during asthma exacerbations caused by hRV infections.
최진영,김진형,Ajit Mahadev Patil,김성범,Erdenebileg Uyangaa,Ferdaus Mohd Altaf Hossain,어성국 대한면역학회 2017 Immune Network Vol.17 No.3
Japanese encephalitis (JE) is neuroinflammation characterized by uncontrolled infiltration of peripheral leukocytes into the central nervous system (CNS). We previously demonstrated exacerbation of JE following CD11chi dendritic cell (DC) ablation in CD11c-DTR transgenic mice. Moreover, CD11chi DC ablation led to abnormal differentiation of CD11b+Ly-6Chi monocytes and enhanced permeability of the blood-brain barrier (BBB), resulting in promoting the progression of JE. Here, we examined changes in lymphoid and myeloid-derived leukocyte subpopulations associated with pro- and anti-inflammation during JE progression. The analyses of this study focused on regulatory CD4+Foxp3+ regulatory T cells (Tregs), IL-17+CD4+ Th17 cells, and CD11b+Ly-6Chi and Ly-6Clo monocytes. CD11chi DC ablation resulted in the accumulation of IL-17+CD4+ Th17 cells in the CNS, thereby leading to lower ratio of Tregs to Th17 cells. This result was corroborated by the higher expression levels of IL-17 and RORgT in CD4+ T cells from the brains of CD11chi DC-ablated mice. In addition, CD11chi DC-ablated mice showed higher frequency and total number of inflammatory CD11b+Ly-6Chi monocytes, whereas CD11b+Ly-6Clo monocytes were detected with lower frequency and total number in CD11chi DC-ablated mice. Furthermore, CD11chi DC ablation altered the phenotype and function of CD11b+Ly-6Clo monocytes, resulting in lower levels of activation marker and anti-inflammatory cytokine (IL-10 and TGF-b) expression. Collectively, these results indicate that CD11chi DC ablation caused an imbalance in CD4+ Th17/Treg cells and CD11b+Ly-6Chi/Ly-6Clo monocytes in the lymphoid tissue and CNS during JE progression. This imbalanced orchestration of pro- and anti-inflammatory leukocytes following CD11chi DC ablation may contribute to the exacerbation of JE.