Real-time tracking of bioluminescent influenza A virus infection in mice

Kim, Jin Hee; Bryant, Hannah; Fiedler, Edward; Cao, TuAnh; Rayner, Jonathan O.

doi:10.1038/s41598-022-06667-w

Cited by 11 publications

(9 citation statements)

References 46 publications

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“…Expression of CD49a but not CD103 has proven to be essential for Trm to confer heterosubtypic immunity and for the cells’ ability to migrate in the tissue whereas CD103 limits migration by reducing the cells’ velocity ( 51 ). CD8 + CD103 - CD49a + T cells expanded and was the major subset at 8 dpi coinciding with the time point when the virus is cleared ( 3 , 33 , 48 ) and clinical signs of infection, i.e. weight loss, are most pronounced.…”

Section: Discussionmentioning

confidence: 82%

“…To study the adaptive immune response after influenza virus infection mice were infected intranasally with PR8 and euthanized at indicated time points up to 7 months post infection. The cardinal symptom is a dose-dependent transient weight loss which reaches its maximum at 7 – 10 dpi ( Figure 1A ) ( 3 , 33 ). A first wave of cell accumulation was observed in lungs and lung-draining MLNs at 3 dpi followed by a second wave at 6 and 8 dpi in MLNs and lungs respectively ( Figure 1B ).…”

Section: Resultsmentioning

confidence: 99%

“…Despite existing vaccines and extensive research, influenza virus continues to pose a global health threat and approximately 291000 – 645000 human influenza A virus-related respiratory deaths are estimated to occur annually ( 1 ). The infection is normally restricted to the respiratory tract resulting in symptoms including cough, fatigue, fever and malaise ( 2 , 3 ). After viral entry, the surface glycoprotein hemagglutinin binds to α2,3-linked sialic acid receptors on ciliated airway epithelial cells ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

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T cell kinetics reveal expansion of distinct lung T cell subsets in acute versus in resolved influenza virus infection

Eriksson

Nylén²,

Grönvik³

2022

Front. Immunol.

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Influenza virus infection is restricted to airway-associated tissues and elicits both cellular and humoral responses ultimately resulting in generation of memory cells able to initiate a rapid immune response against re-infections. Resident memory T cells confer protection at the site of infection where lung-resident memory T cells are important for protecting the host against homologous and heterologous influenza virus infections. Mapping kinetics of local and systemic T cell memory formation is needed to better understand the role different T cells have in viral control and protection. After infecting BALB/c mice with influenza virus strain A/Puerto Rico/8/1934 H1N1 the main proportion of activated T cells and B cells expressing the early activation marker CD69 was detected in lungs and lung-draining mediastinal lymph nodes. Increased frequencies of activated cells were also observed in the peripheral lymphoid organs spleen, inguinal lymph nodes and mesenteric lymph nodes. Likewise, antigen-specific T cells were most abundant in lungs and mediastinal lymph nodes but present in all organs studied. CD8+CD103-CD49a+ lung-resident T cells expanded simultaneously with timing of viral clearance whereas CD8+CD103+CD49a+ lung-resident T cells was the most abundant subset after resolution of infection and antigen-specific, lung-resident T cells were detected up to seven months after infection. In conclusion, the results in this detailed kinetic study demonstrate that influenza virus infection elicits adaptive immune responses mainly in respiratory tract-associated tissues and that distinct subsets of lung-resident T cells expand at different time points during infection. These findings contribute to the understanding of the adaptive immune response locally and systemically following influenza virus infection and call for further studies on the roles of the lung-resident T cell subsets.

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Section: Discussionmentioning

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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T cell kinetics reveal expansion of distinct lung T cell subsets in acute versus in resolved influenza virus infection

Eriksson

Nylén²,

Grönvik³

2022

Front. Immunol.

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“…Our imaging studies indicated that lung IAV-specific CD4 T cells are likely to have multiple interactions with APCs during IAV infection. In mice, IAV is cleared within the first ten days of an infection 26, 27 but antigen can be presented to CD4 T cells for at least 35 days post-infection 34 . We wanted to investigate whether presentation of antigen in the lung was important in the generation of memory CD4 T cell function and location.…”

Section: Resultsmentioning

confidence: 99%

Lung influenza virus specific memory CD4 T cell location and optimal cytokine production are dependent on interactions with lung antigen-presenting cells

Hargrave,

Worrell,

Pirillo

et al. 2023

Preprint

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Influenza A virus (IAV) infection leads to the formation of mucosal memory CD4 T cells that can protect the host. An in-depth understanding of the signals that shape memory cell development is required for more effective vaccine design. We have examined the formation of memory CD4 T cells in the lung following IAV infection of mice, characterising changes to the lung architecture and immune cell composition. IAV-specific CD4 T cells were found throughout the lung at both primary and memory time points. These cells were found near lung airways and in close contact with a range of immune cells including macrophages, dendritic cells, and B cells. Interactions between lung IAV-specific CD4 T cells and MHCII+ cells during the primary immune response were important in shaping the subsequent memory pool. Treatment with an anti-MHCII blocking antibody increased the proportion of memory CD4 T cells found at lung airways but reduced interferon-gamma expression by IAV-specific immunodominant memory CD4 T cells. The immunodominant CD4 T cells expressed higher levels of PD1 than other IAV-specific CD4 T cells and PD1+ memory CD4 T cells were located further away from MHCII+ cells than their PD1-negative counterparts. This distinction in location was lost in mice treated with anti-MHCII antibody. These data suggest that sustained antigen presentation in the lung impacts on the formation of memory CD4 T cells by regulating their cytokine production and location.

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“…Validation of reduced cell toxicity could be accomplished using an MTT assay. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay is routinely used to assess cell metabolic activity, viability, membrane integrity, and proliferation, all of which are indicators of overall cell health [15]. Here, several different human cell lines could be tested to determine the effects of either boronium salt on both cell viability and cell proliferation.…”

Section: Overall Assessmentmentioning

confidence: 99%

Boronium Salt as an Antiviral Agent against Enveloped Viruses Influenza A and SARS-CoV-2

Ravine

Rayner

Roberts

et al. 2022

Applied Biosciences

Self Cite

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Quaternary ammonium compounds (QACs) are routinely used as disinfectants in a variety of settings. They are generally effective against a wide range of microbes but often exhibit undesirable toxicity. Consequently, companies are constantly seeking alternatives to QACs that are just as effective but with reduced health and environmental hazards. Two boronium salt derivatives were tested against influenza A and SARS-CoV-2 viruses. One salt possessed a terminal benzyl group, while the other lacked the same terminal benzyl group. Both salts demonstrated virus inactivation similar to a commercial QAC disinfectant. The non-benzylated form exhibited the same cell toxicity profile as the QAC. However, the benzylated form displayed less cell toxicity than both the non-benzylated form and QAC. These results suggest that the boronium salts may be suitable for use as a disinfecting agent against enveloped viruses in lieu of using a QAC. Continued evaluation of the boronium salts is warranted to determine the lowest effective concentration capable of effectively controlling influenza A and SARS-CoV-2 viruses that also demonstrates low cytotoxicity.

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Real-time tracking of bioluminescent influenza A virus infection in mice

Cited by 11 publications

References 46 publications

T cell kinetics reveal expansion of distinct lung T cell subsets in acute versus in resolved influenza virus infection

T cell kinetics reveal expansion of distinct lung T cell subsets in acute versus in resolved influenza virus infection

Lung influenza virus specific memory CD4 T cell location and optimal cytokine production are dependent on interactions with lung antigen-presenting cells

Boronium Salt as an Antiviral Agent against Enveloped Viruses Influenza A and SARS-CoV-2

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