IL-10 inhibits neuraminidase-activated TGF-β and facilitates Th1 phenotype during early phase of infection

Dutta, Alo; Huang, Ching-Tai; Chen, Tse–Ching; Lin, Chun‐Yen; Chiu, Cheng-Hsun; Lin, Yung‐Chang; Chang, Chingching; He, Yueh-Chia

doi:10.1038/ncomms7374

Cited by 28 publications

(50 citation statements)

References 49 publications

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“…With the adoptive transfer of HA antigen-specific CD4+ and CD8+ T cells, experiments in our transgenic mouse model revealed that antigen-specific T cell response elevates the level of protection with sterilization effect from the level with accelerated virus clearance only. Although the physiological significance is a concern with unusually high precursor frequency of T cells of certain antigen specificity in adoptive transfer approach, we and others have demonstrated that the frequency of specific T cells with adoptive transfer is not appreciably different from those with physiological T cell expansion2425515253. We also have identified LAG-3 as the target for cancer immunotherapy with this approach and anti-LAG-3 has been in phase I clinical trial since 2013 (ref.…”

Section: Discussionmentioning

confidence: 86%

“…As there should be virus antigen shedding with the second possibility, we tested virus antigen shedding by the viruses of lethal challenge in pre-infected mice through antigen-driven activation of influenza hemagglutinin (HA) antigen-specific 6.5 CD4+ T cells. At first, naïve HA-specific 6.5 CD4+ T cells were adoptively transferred on the same day with first virus exposure2425. Virus antigens of the first intranasal inoculation (pre-infection) activated adoptively transferred naïve HA-specific 6.5 CD4+ T cells on day 7 after pre-infection (Before, Fig.…”

Section: Resultsmentioning

confidence: 99%

“…For first virus exposure, indicated inoculums of live PR8 (A/PR/8/34) strain of H1N1 influenza A virus in 50 μl of PBS were inoculated intranasally or injected through thigh muscle under light anesthesia2425. Inoculum of 1.25 × 10 4 PFU, also in 50 μl of PBS, under light anesthesia was used for the lethal challenge.…”

Section: Methodsmentioning

confidence: 99%

“…We measured live virus in organs of influenza virus infected mice using a modified Madin Darby canine kidney cell (MDCK; The American Type Culture Collection) plaque assay2425. Organs are collected at the indicated times in 1 ml DMEM, snap frozen in liquid nitrogen and stored at −80 °C until they are ready for use.…”

Section: Methodsmentioning

confidence: 99%

“…The functional neutralizing antibody against influenza was quantified by plaque reduction assay as described in our previous publication2425. In brief, sera or lung lysates from mice are collected on day 7- post vaccination.…”

Section: Methodsmentioning

confidence: 99%

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Sterilizing immunity to influenza virus infection requires local antigen-specific T cell response in the lungs

Dutta

Huang

Lin

et al. 2016

Sci Rep

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Sterilizing immunity is a unique immune status, which prevents effective virus infection into the host. It is different from the immunity that allows infection but with subsequent successful eradication of the virus. Pre-infection induces sterilizing immunity to homologous influenza virus challenge in ferret. In our antigen-specific experimental system, mice pre-infected with PR8 influenza virus through nasal route are likewise resistant to reinfection of the same strain of virus. The virus is cleared before establishment of effective infection. Intramuscular influenza virus injection confers protection against re-infection with facilitated virus clearance but not sterilizing immunity. Pre-infection and intramuscular injection generates comparable innate immunity and antibody response, but only pre-infection induces virus receptor reduction and efficient antigen-specific T cell response in the lungs. Pre-infection with nH1N1 influenza virus induces virus receptor reduction but not PR8-specific T cell immune response in the lungs and cannot prevent infection of PR8 influenza virus. Pre-infection with PR8 virus induced PR8-specific T cell response in the lungs but cannot prevent infection of nH1N1 virus either. These results reveal that antigen-specific T cell immunity is required for sterilizing immunity.

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Section: Discussionmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Sterilizing immunity to influenza virus infection requires local antigen-specific T cell response in the lungs

Dutta

Huang

Lin

et al. 2016

Sci Rep

Self Cite

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Influenza A Virus Infection, Innate Immunity, and Childhood

et al. 2015

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Infection with influenza A virus is responsible for considerable morbidity and mortality in children worldwide. While it is apparent that adequate activation of the innate immune system is essential for pathogen clearance and host survival, an excessive inflammatory response to infection is detrimental to the young host. A review of the literature indicates that innate immune responses change throughout childhood. Whether these changes are genetically programmed or triggered by environmental cues is unknown. The objectives of this review are to summarize the role of innate immunity in influenza A virus infection in the young child and to highlight possible differences between children and adults that may make children more susceptible to severe influenza A infection. A better understanding of age-related differences in innate immune signaling will be essential to improve care for this high-risk population.Influenza A virus (IAV) is a highly contagious RNA virus that causes respiratory tract infections in humans and animals. Seasonal IAV is responsible for considerable disease worldwide, with the World Health Organization estimating 3 to 5 million severe cases of IAV each year and approximately 250 000 to 500 000 deaths. 1 Pandemics threaten to affect significantly more people. During the 1918 pandemic, it is estimated that IAV was responsible for 50 to 100 million deaths. 2 The burden of IAV infection is highest in children, the elderly, and persons with chronic medical conditions. Each year, IAV infection affects up to 40% of children younger than 5 years in the United States and 90 million

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Type I IFN signaling facilitates the development of IL‐10‐producing effector CD8⁺ T cells during murine influenza virus infection

et al. 2016

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Recent evidence has suggested that IL-10-producing effector CD8+ T cells play an important role in regulating excessive inflammation during acute viral infections. However, the cellular and molecular cues regulating the development of IL-10-producing effector CD8+ T cells are not completely defined. Here we show that type I interferons (IFNs) are required for the development of IL-10-producing effector CD8+ T cells during influenza virus infection. We find that type I IFNs can enhance IL-27 production by lung antigen presenting cells, thereby facilitating IL-10-producing CD8+ T cell development through a CD8+ T cell non-autonomous way. Surprisingly, we also demonstrate that direct type I IFN signaling in CD8+ T cells is required for the maximal generation of IL-10-producing CD8+ T cells. Type I IFN signaling in CD8+ T cells, in cooperation with IL-27 and IL-2 signaling, promotes and sustains the expression of IRF4 and Blimp-1, two transcription factors required for the production of IL-10 by effector CD8+ T cells. Our data have revealed a critical role of the innate antiviral effector cytokines in regulating the production of a regulatory cytokine by effector CD8+ T cells during respiratory virus infection. The potential implications of these findings for influenza virus infection are also discussed.

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IL-10 inhibits neuraminidase-activated TGF-β and facilitates Th1 phenotype during early phase of infection

Cited by 28 publications

References 49 publications

Sterilizing immunity to influenza virus infection requires local antigen-specific T cell response in the lungs

Sterilizing immunity to influenza virus infection requires local antigen-specific T cell response in the lungs

Influenza A Virus Infection, Innate Immunity, and Childhood

Type I IFN signaling facilitates the development of IL‐10‐producing effector CD8⁺ T cells during murine influenza virus infection

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IL-10 inhibits neuraminidase-activated TGF-β and facilitates Th1 phenotype during early phase of infection

Cited by 28 publications

References 49 publications

Sterilizing immunity to influenza virus infection requires local antigen-specific T cell response in the lungs

Sterilizing immunity to influenza virus infection requires local antigen-specific T cell response in the lungs

Influenza A Virus Infection, Innate Immunity, and Childhood

Type I IFN signaling facilitates the development of IL‐10‐producing effector CD8+ T cells during murine influenza virus infection

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Type I IFN signaling facilitates the development of IL‐10‐producing effector CD8⁺ T cells during murine influenza virus infection