Interferon-γ promotes monocyte-mediated lung injury during influenza infection

Schmit, Taylor; Guo, Kai; Tripathi, Jitendra Kumar; Wang, Zhihan; McGregor, Brett A.; Klomp, Mitch; Ambigapathy, Ganesh; Mathur, Ramkumar; Hur, Junguk; Pichichero, Michael E.; Kolls, Jay K.; Khan, M. Nadeem

doi:10.1016/j.celrep.2022.110456

Cited by 41 publications

(37 citation statements)

References 61 publications

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“…Despite their beneficial role in mediating viral clearance, CD8 + T cells might promote immunopathology in some situations. This phenomenon is well recognized in the mouse model of respiratory syncytial virus (RSV) infection; it has also been observed in several other virus-infection models, including influenza virus ( 33 – 36 ) and murine adenovirus models ( 37 ).…”

Section: Cd8 + T Cells Might Occasionally Contribu...mentioning

confidence: 78%

Considerations of CD8+ T Cells for Optimized Vaccine Strategies Against Respiratory Viruses

Hirai

Yoshioka

2022

Front. Immunol.

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The primary goal of vaccines that protect against respiratory viruses appears to be the induction of neutralizing antibodies for a long period. Although this goal need not be changed, recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have drawn strong attention to another arm of acquired immunity, CD8+ T cells, which are also called killer T cells. Recent evidence accumulated during the coronavirus disease 2019 (COVID-19) pandemic has revealed that even variants of SARS-CoV-2 that escaped from neutralizing-antibodies that were induced by either infection or vaccination could not escape from CD8+ T cell-mediated immunity. In addition, although traditional vaccine platforms, such as inactivated virus and subunit vaccines, are less efficient in inducing CD8+ T cells, newly introduced platforms for SARS-CoV-2, namely, mRNA and adenoviral vector vaccines, can induce strong CD8+ T cell-mediated immunity in addition to inducing neutralizing antibodies. However, CD8+ T cells function locally and need to be at the site of infection to control it. To fully utilize the protective performance of CD8+ T cells, it would be insufficient to induce only memory cells circulating in blood, using injectable vaccines; mucosal immunization could be required to set up CD8+ T cells for the optimal protection. CD8+ T cells might also contribute to the pathology of the infection, change their function with age and respond differently to booster vaccines in comparison with antibodies. Herein, we overview cutting-edge ideas on CD8+ T cell-mediated immunity that can enable the rational design of vaccines for respiratory viruses.

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Section: Cd8 + T Cells Might Occasionally Contribu...mentioning

confidence: 78%

Considerations of CD8+ T Cells for Optimized Vaccine Strategies Against Respiratory Viruses

Hirai

Yoshioka

2022

Front. Immunol.

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“…Under LPS induction, there was a significant increase in pro‐inflammatory factors, IFN‐γ and TNF‐α, but their levels were reduced in the combined therapy group. Recently, in the in vitro study of Schmit et al, 40 the authors demonstrated that IFN‐γ derived from CD8 + T cells promoted the recruitment of the monocyte phenotype with CCR2 + and the expression of CCL2 in lungs with ALI. On the other side, high expression of TNF‐α in sepsis leads to systemic symptoms and NO release by activating phagocytic cells such as macrophages and neutrophils 13,41 …”

Section: Discussionmentioning

confidence: 99%

Green synthesis of gold nanoparticles modulates lipopolysaccharide‐induced lung inflammation in Wistar rats

Casagrande

Porto

Colares

et al. 2023

Basic Clin Pharma Tox

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This study aimed to investigate the effect of intranasal treatment of gold nanoparticles (GNPs) and Curcumin (Cur) on the lipopolysaccharide (LPS)-induced acute pulmonary inflammatory response. A single intraperitoneal injection of LPS (0.5 mg/Kg) was performed, and the animals in the Sham group were injected with 0.9% saline. Treatment was daily intranasally with GNPs (2.5 mg/L), Cur (10 mg/kg) and GNP-Cur started 12 h after LPS administration and ended on the seventh day. The results show that the treatment performed with GNP-Cur was the most effective to attenuate the action of proinflammatory cytokines, and a lower leukocyte count in the bronchoalveolar lavage, in addition to positively regulating anti-inflammatory cytokines in relation to other groups. As a result, it promoted an oxirreductive balanced environment in the lung tissue, providing a histological outcome with a reduction in inflammatory cells and greater alveolar area. The group treated with GNPs-Cur was superior to the other groups, with better anti-inflammatory activity and reduced oxidative stress, resulting in less morphological damage to lung tissue. In conclusion, the use of reduced GNPs with curcumin demonstrates promising effects in the control of the acute inflammatory response, helping to protect the lung tissue at the biochemical and morphological levels.

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“…Mononuclear phagocytes, particularly macrophages and monocytes, are known for their functional plasticity in response to cytokine milieu ( 40 ). In agreement, here we show that mononuclear phagocytes play a dominant role in driving TNF-α production and ARDS pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

IFN-γ transforms the transcriptomic landscape and triggers myeloid cell hyperresponsiveness to cause lethal lung injury

et al. 2022

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Acute Respiratory Distress Syndrome (ARDS) is an inflammatory disease that is associated with high mortality but no specific treatment. Our understanding of initial events that trigger ARDS pathogenesis is limited. We have developed a mouse model of inflammatory lung injury by influenza and methicillin-resistant Staphylococcus aureus (MRSA) coinfection plus daily antibiotic therapy. Using this pneumonic ARDS model, here we show that IFN-γ receptor signaling drives inflammatory cytokine storm and lung tissue damage. By single-cell RNA sequencing (scRNA-seq) analysis, we demonstrate that IFN-γ signaling induces a transcriptional shift in airway immune cells, particularly by upregulating macrophage and monocyte expression of genes associated with inflammatory diseases. Further evidence from conditional knockout mouse models reveals that IFN-γ receptor signaling in myeloid cells, particularly CD11c+ mononuclear phagocytes, directly promotes TNF-α hyperproduction and inflammatory lung damage. Collectively, the findings from this study, ranging from cell-intrinsic gene expression to overall disease outcome, demonstrate that influenza-induced IFN-γ triggers myeloid cell hyperresponsiveness to MRSA, thereby leading to excessive inflammatory response and lethal lung damage during coinfection.

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Interferon-γ promotes monocyte-mediated lung injury during influenza infection

Cited by 41 publications

References 61 publications

Considerations of CD8+ T Cells for Optimized Vaccine Strategies Against Respiratory Viruses

Considerations of CD8+ T Cells for Optimized Vaccine Strategies Against Respiratory Viruses

Green synthesis of gold nanoparticles modulates lipopolysaccharide‐induced lung inflammation in Wistar rats

IFN-γ transforms the transcriptomic landscape and triggers myeloid cell hyperresponsiveness to cause lethal lung injury

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