A gammaherpesvirus licenses CD8 T cells to protect the host from pneumovirus-induced immunopathologies

Dourcy, Mickaël; Maquet, Céline; Dams, Lorène; Gilliaux, Gautier; Javaux, Justine; Desmecht, Daniël; Mack, Matthias; Dewals, Benjamin G; Machiels, Bénédicte; Gillet, Laurent

doi:10.1038/s41385-020-0293-7

Cited by 6 publications

(3 citation statements)

References 58 publications

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“…7). A similar boost of heterologous immunity was recently made in the context of other viral infections by our group (38). Considering these observations, development of vectored-vaccines based on replication competent AdVs could also be advantageous for an improved T cell immune response.…”

Section: Discussionsupporting

confidence: 61%

A single oral immunization with a replication-competent adenovirus-vectored vaccine protects mice from influenza respiratory infection

Goffin¹,

Hemmi

Machiels³

et al. 2021

Preprint

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The development of effective and flexible vaccine platforms is a major public health challenge as recently highlighted by the COVID-19 pandemic. Adenoviruses (AdVs) are easy to produce and have a good safety and efficacy profile when administered orally as demonstrated by the long-term use of oral AdV 4 and 7 vaccines in the US military. These viruses therefore appear to be the ideal backbone for the development of oral replicative vector vaccines. However, research on these vaccines is limited by the ineffective replication of human AdVs in laboratory animals. The use of mouse AdV type 1 (MAV-1) in its natural host allows infection to be studied under replicative conditions. Here, we orally vaccinated mice with MAV-1 vectors expressing the full length or the headless hemagglutinin (HA) of influenza to assess the protection conferred against an intranasal challenge of influenza. We showed that while the headless HA vector did not generate a significant humoral or cellular immune response to influenza, a single oral immunisation with the full-length HA vaccine generated influenza-specific and neutralizing antibodies and completely protected the mice against clinical signs and viral replication.

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Section: Discussionsupporting

confidence: 61%

A single oral immunization with a replication-competent adenovirus-vectored vaccine protects mice from influenza respiratory infection

Goffin¹,

Hemmi

Machiels³

et al. 2021

Preprint

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“…Activation and proliferation of antigen-independent bystander CD8 + T cells and their function during subsequent infections have remained controversial. Though some studies have assigned them a role during viral infections [35,36], other studies suggested that bystander activation of CD8 + T cells is insignificant in terms of functional roles [37][38][39][40]. Recently, however, studies have demonstrated that the host priming by a pathogen induced a long-term infiltration of CD8 + T cells in the lungs.…”

Section: Discussionmentioning

confidence: 99%

Gammaherpesvirus Alters Alveolar Macrophages According to the Host Genetic Background and Promotes Beneficial Inflammatory Control over Pneumovirus Infection

Gilliaux

Desmecht

2022

Viruses

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Human respiratory syncytial virus (hRSV) infection brings a wide spectrum of clinical outcomes, from a mild cold to severe bronchiolitis or even acute interstitial pneumonia. Among the known factors influencing this clinical diversity, genetic background has often been mentioned. In parallel, recent evidence has also pointed out that an early infectious experience affects heterologous infections severity. Here, we analyzed the importance of these two host-related factors in shaping the immune response in pneumoviral disease. We show that a prior gammaherpesvirus infection improves, in a genetic background-dependent manner, the immune system response against a subsequent lethal dose of pneumovirus primary infection notably by inducing a systematic expansion of the CD8+ bystander cell pool and by modifying the resident alveolar macrophages (AMs) phenotype to induce immediate cyto/chemokinic responses upon pneumovirus exposure, thereby drastically attenuating the host inflammatory response without affecting viral replication. Moreover, we show that these AMs present similar rapid and increased production of neutrophil chemokines both in front of pneumoviral or bacterial challenge, confirming recent studies attributing a critical antibacterial role of primed AMs. These results corroborate other recent studies suggesting that the innate immunity cells are themselves capable of memory, a capacity hitherto reserved for acquired immunity.

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“…MuHV-4 infection has been shown to train immunity against various heterologous infections ( 54 , 55 ). In addition to triggering regulatory pathways to dampen specific antiviral defenses, γHVs license CD8 ( 56 ), and potentially CD4, T cells to protect their own niche against heterologous pathogens. Here, we provide evidence supporting a role for γHV-imprinted MOs in the activation of CD4 T cells while finely regulating their cytotoxic and degranulation capacities.…”

Section: Discussionmentioning

confidence: 99%

Ly6C ^hi monocytes balance regulatory and cytotoxic CD4 T cell responses to control virus-induced immunopathology

et al. 2022

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Gammaherpesviruses (γHVs) have coevolved with their host, leading to a remarkably high infection prevalence and establishment of latency. The lifelong persistence of γHVs in hosts appears to broadly shape host immunity, and we show here that pulmonary infection with Murid herpesvirus 4 (MuHV-4), a mouse γHV, drives the recruitment of Ly6C hi monocytes (MOs) into the airway, thereby modulating the host immune response. The absence of Ly6C hi MOs is associated with severe virus-induced immunopathology and the systemic release of inflammatory mediators. Mechanistically, MuHV-4–imprinted MOs recruit CD4 T cells to the airways and trigger immunosuppressive signaling pathways through the PD-L1/PD-1 axis, thereby dampening the deleterious activation of cytotoxic CD4 T cells. These results uncover a role for Ly6C hi MOs in modulating CD4 T cell functions and reveal pathways that could be targeted therapeutically to reduce detrimental immunopathological responses associated with respiratory viral infections.

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A gammaherpesvirus licenses CD8 T cells to protect the host from pneumovirus-induced immunopathologies

Cited by 6 publications

References 58 publications

A single oral immunization with a replication-competent adenovirus-vectored vaccine protects mice from influenza respiratory infection

A single oral immunization with a replication-competent adenovirus-vectored vaccine protects mice from influenza respiratory infection

Gammaherpesvirus Alters Alveolar Macrophages According to the Host Genetic Background and Promotes Beneficial Inflammatory Control over Pneumovirus Infection

Ly6C ^hi monocytes balance regulatory and cytotoxic CD4 T cell responses to control virus-induced immunopathology

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A gammaherpesvirus licenses CD8 T cells to protect the host from pneumovirus-induced immunopathologies

Cited by 6 publications

References 58 publications

A single oral immunization with a replication-competent adenovirus-vectored vaccine protects mice from influenza respiratory infection

A single oral immunization with a replication-competent adenovirus-vectored vaccine protects mice from influenza respiratory infection

Gammaherpesvirus Alters Alveolar Macrophages According to the Host Genetic Background and Promotes Beneficial Inflammatory Control over Pneumovirus Infection

Ly6C hi monocytes balance regulatory and cytotoxic CD4 T cell responses to control virus-induced immunopathology

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Product

Resources

About

Ly6C ^hi monocytes balance regulatory and cytotoxic CD4 T cell responses to control virus-induced immunopathology