ABSTRACT
There are overwhelming reports on the promotional effect of hypoxia on the malignant behavior of various forms of cancer cells. This has been proposed and tested exhaustively in the light of cancer immunotherapy. However, there could be more interesting functions of a hypoxic cellular micro-environment than malignancy. There is a highly intricate crosstalk between hypoxia inducible factor (HIF), a transcriptional factor produced during hypoxia, and nuclear factor kappa B (NF-κB) which has been well characterized in various immune cell types. This important crosstalk shares common activating and inhibitory stimuli, regulators, and molecular targets. Impaired hydroxylase activity contributes to the activation of HIFs. Inflammatory ligands activate NF-κB activity, which leads to the expression of inflammatory and anti-apoptotic genes. The eventual sequelae of the interaction between these two molecular players in immune cells, either bolstering or abrogating functions, is largely cell-type dependent. Importantly, this holds promise for interesting therapeutic interventions against several infectious diseases, as some HIF agonists have helped prevent immune-related diseases. Hypoxia and inflammation are common features of infectious diseases. Here, we highlighted the role of this crosstalk in the light of functional immunity against infection and inflammation, with special focus on various innate and adaptive immune cells. Particularly, we discussed the bidirectional effects of this crosstalk in the regulation of immune responses by monocytes/macrophages, dendritic cells, neutrophils, B cells, and T cells. We believe an advanced understanding of the interplay between HIFs and NF-kB could reveal novel therapeutic targets for various infectious diseases with limited treatment options.
Subject(s)
Communicable Diseases , NF-kappa B , Humans , Leukocytes , Immunotherapy , HypoxiaABSTRACT
Several months after the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), cases of re-infection after recovery were reported. The extent and duration of protective immunity after SARS-CoV-2 infection is not fully understood. As such, the possibility of re-infection with SARS-CoV-2. Furthermore, cases of re-infection were mainly due to different variants or mutant SARS-CoV-2. Following the fast and pandemic-scale spread of COVID-19, mutations in SARS-CoV-2 have raised new diagnostic challenges which include the redesign of the oligonucleotide sequences used in RT-PCR assays to avoid potential primer-sample mismatches, and decrease sensitivities. Since the initial wave of the pandemic, some regions had experienced fresh outbreaks, predisposing people to be susceptible to SARS-CoV-2 re-infection. Hence, this article sought to offer detailed biology of SARS-CoV-2 re-infections and their implications on immune response milieu, diagnostic laboratory tests and control measures against COVID-19.
ABSTRACT
The incidence and case-fatality rates (CFRs) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, the etiological agent for Coronavirus Disease 2019 (COVID-19), have been rising unabated. Even though the entire world has been implementing infection prevention and control measures, the pandemic continues to spread. It has been widely accepted that preventive vaccination strategies are the public health measures for countering this pandemic. This study critically reviews the latest scientific advancement in genomics, replication pattern, pathogenesis, and immunopathology of SARS-CoV-2 infection and how these concepts could be used in the development of vaccines. We also offer a detailed discussion on the anticipated potency, efficacy, safety, and pharmaco-economic issues that are and will be associated with candidate COVID-19 vaccines.
