MxA suppresses TAK1-IKK alpha/beta-NF-kappa B mediated inflammatory cytokine production to facilitate Mycobacterium tuberculosis infection
JOURNAL OF INFECTION
Authors: Zhou, Xinying; Zhang, Lijie; Lie, Linmiao; Zhang, Zelin; Zhu, Bo; Yang, Jiahui; Gao, Yuchi; Li, Pengfei; Huang, Yingqi; Xu, Hui; Li, Yanfen; Du, Xialin; Zhou, Chaoying; Hu, Shengfeng; Wen, Qian; Zhong, Xiao-Ping; Ma, Li
Abstract
Objectives: Interferons (IFNs) play multifunctional roles in host defense against infectious diseases by inducing IFN-stimulated genes (ISGs). However, little is known about how ISGs regulate host immune response to Mycobacterium tuberculosis (Mtb) infection, the major cause of tuberculosis (TB). Methods: We thus profiled the potential effects and mechanisms of eight Mtb-induced ISGs on Mtb infection by RNA interference in human macrophages (W phi s) derived from peripheral blood monocytes (hMDMs) and THP-1 cell line derived W phi s (THP-1-W phi s). Results: MxA silencing significantly decreased intracellular Mtb infection in M phi s. Mechanistically, MxA silencing promoted inflammatory cytokines IL-1 beta, IL-6 and TNF-alpha production, and induced NF-kappa B p65 activation. Pharmacological inhibition of NF-kappa B p65 activation or gene silencing of NF-kappa B p65 blocked the increased production of IL-1 beta, IL-6 and TNF-alpha and restored Mtb infection by MxA silencing. Furthermore, pharmacological inhibition of TAK1 and IKK alpha/beta blocked NF-kappa B p65 activation and subsequent production of pro-inflammatory cytokines by MxA silencing. Isoniazid (INH) treatment and MxA silencing could promote TAK1-IKK alpha/beta-NF-kappa B signaling pathway activation and combat Mtb infection independently. Conclusions: Our results reveal a novel role of MxA in regulating TAK1-IKK alpha/beta-NF-kappa B signaling activation and production of antimicrobial inflammatory cytokines upon Mtb infection, providing a potential target for clinical treatment of TB. (C) 2020 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Histopathological Spectrum of Lesions in Lungs on Post-mortem Specimen in a Tertiary Centre of Bastar Region-A Retrospective Study
JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH
Authors: Dhruw, Deepika; Chikhlikar, Kasturi; Nayak, Kalpana; Thakur, Nitya; Singh, Bhanupratap; Meshram, Avinash
Abstract
Introduction: Lungs are the major organ involved in a number of infectious, inflammatory and occupational disease, secondarily involved in almost all form of terminal disease. So many people around the world suffer from preventable Lung disease. Many a times it has been found that when gross pathology could not help to evaluate cause of death, histopathology provide the valuable information. Aim: To study the spectrum of histopathological finding in lung autopsy and the incidental findings identified during histopathological examination gain a prime importance in academic and research purpose. Materials and Methods: This was a retrospective study done in the Department of Pathology, Lt B.R. K. M G.M. C, Bastar, Chhattisgarh, India, over a period of 10 years i.e., from January 2010 to December 2019. The study consisted of Lung specimens (474 cases) from medico-legal autopsies, irrespective of their age and sex, received during this period. Gross and Microscopic features were documented, and diagnosis was made. The results were analysed based on gross findings and the histopathological examination. Results: Among 474 cases studied during period of 10 years, maximum cases were seen in 30-39 (141 cases) years of age group. Males were more commonly affected 345 ( 73%) as compared to Females 129 (27%). Pathological findings of Lung were seen in 441 cases, of which Pulmonary Oedema with Congestion was found in 352 cases, along with Intra-alveolar Haemorrhage in 41 cases, Bronchopneumonia in 14 cases, Lobar Pneumonia in 11 cases, seven cases of Tuberculosis, Interstitial Pneumonia in seven cases, Vegetative material in three cases, Emphysema in three cases, Aspiration pnuemonitis in two cases and one case of Chronic Bronchitis. Conclusion: Autopsy study of lung specimens gives valuable information, improves clinical diagnosis and provides diagnostic setup for better clinical assessment. Histopathological examination proves to be the great diagnostic tool in the identification of lung lesions which were incidental finding or direct cause of death. Limitation was non-availability of large specimens, detailed clinical history and autolysis of the organ.