Related Experiment Video
Updated: Sep 7, 2025
Real-time Monitoring of Mitochondrial Respiration in Cytokine-differentiated Human Primary T Cells
Published on: October 19, 2021
Mitochondrial cyclophilin D promotes disease tolerance by licensing NK cell development and IL-22 production against
Jeffrey Downey1, Haley E Randolph2, Erwan Pernet1
1Department of Medicine, McGill University Health Centre, McGill International TB Centre, Meakins-Christie Laboratories, McGill University, 1001 Decarie Boulevard, Montreal, QC H4A 3J1, Canada; Department of Pathology, McGill University Health Centre, McGill International TB Centre, Meakins-Christie Laboratories, McGill University, 1001 Decarie Boulevard, Montreal, QC H4A 3J1, Canada; Department of Microbiology & Immunology, McGill University Health Centre, McGill International TB Centre, Meakins-Christie Laboratories, McGill University, 1001 Decarie Boulevard, Montreal, QC H4A 3J1, Canada.
Abstract:
Severity of pulmonary viral infections, including influenza A virus (IAV), is linked to excessive immunopathology, which impairs lung function. Thus, the same immune responses that limit viral replication can concomitantly cause lung damage that must be countered by largely uncharacterized disease tolerance mechanisms. Here, we show that mitochondrial cyclophilin D (CypD) protects against IAV via disease tolerance. CypD-/- mice are significantly more susceptible to IAV infection despite comparable antiviral immunity. This susceptibility results from damage to the lung epithelial barrier caused by a reduction in interleukin-22 (IL-22)-producing natural killer (NK) cells. Transcriptomic and functional data reveal that CypD-/- NK cells are immature and have altered cellular metabolism and impaired IL-22 production, correlating with dysregulated bone marrow lymphopoiesis. Administration of recombinant IL-22 or transfer of wild-type (WT) NK cells abrogates pulmonary damage and protects CypD-/- mice after IAV infection. Collectively, these results demonstrate a key role for CypD in NK cell-mediated disease tolerance.
Related Concept Videos
01:24T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
01:29Immune Response Against Viral Pathogens
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
01:27Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
02:26NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
01:25Immune Surveillance by NK Cells and Phagocytes
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
01:28Cells of the Innate Immune Response
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...