Role of γδ T cells in controlling viral infections with a focus on influenza virus: implications for designing novel therapeutic approaches

Abstract

Background Influenza virus infection is among the most detrimental threats to the health of humans and some animals, infecting millions of people annually all around the world and in many thousands of cases giving rise to pneumonia and death. All those health crises happen despite previous and recent developments in anti-influenza vaccination, suggesting the need for employing more sophisticated methods to control this malign infection. Main body The innate immunity modules are at the forefront of combating against influenza infection in the respiratory tract, among which, innate T cells, particularly gamma-delta (γδ) T cells, play a critical role in filling the gap needed for adaptive immune cells maturation, linking the innate and adaptive immunity together. Upon infection with influenza virus, production of cytokines and chemokines including CCL3, CCL4, and CCL5 from respiratory epithelium recruits γδ T cells at the site of infection in a CCR5 receptor-dependent fashion. Next, γδ T cells become activated in response to influenza virus infection and produce large amounts of proinflammatory cytokines, especially IL-17A. Regardless of γδ T cells’ roles in triggering the adaptive arm of the immune system, they also protect the respiratory epithelium by cytolytic and non-cytolytic antiviral mechanisms, as well as by enhancing neutrophils and natural killer cells recruitment to the infection site. Conclusion In this review, we explored varied strategies of γδ T cells in defense to influenza virus infection and how they can potentially provide balanced protective immune responses against infected cells. The results may provide a potential window for the incorporation of intact or engineered γδ T cells for developing novel antiviral approaches or for immunotherapeutic purposes.

mRNA COVID-19 vaccine elicits potent adaptive immune response without the persistent inflammation seen in SARS-CoV-2 infection

“…γδ T cells are a subset of unconventional non-MHC restricted innate-like T cells with cytotoxic effector functions and ability to regulate other immune cells (Lawand et al, 2017;Sabbaghi et al, 2020). Transcriptional analysis revealed expression of genes associated with cytotoxic effector functions in the γδ T cells from COVID-19 patients, a feature that was not observed in γδ T cells from HCs or vaccinated individuals (Supplemental Fig.…”

Too young to die? How aging affects cellular innate immune responses to influenza virus and disease severity

“…For example, unconventional T cells that encompass NKT cells, gamma delta T cells and mucosalassociated invariant T cells, share features of innate and adaptive immunity, being able to respond to both antigen-specific and cytokine stimuli [207]. Although the cognate antigens for these cells are not necessarily produced during IAV infections, unconventional T cells can rapidly respond to induced proinflammatory cytokines such as IL-18 and IL-12, which can be elevated with aging, and release a wide array of cytokines that can influence the succeeding adaptive immune response and therefore the course of the disease [27,[207][208][209][210]. Therefore, unconventional T cells as well as the innate immune cells highlighted in this review that significantly contribute to IAV immunity and recovery from IAV infection, warrant further investigation in this setting.…”

Decreased Frequencies of Gamma/Delta T Cells Expressing Th1/Th17 Cytokine, Cytotoxic, and Immune Markers in Latent Tuberculosis-Diabetes/Pre-Diabetes Comorbidity

“…Recent data suggest that reduced frequencies in gd T cells are associated with reduced survival rate and increased lung injury upon H5N1 respiratory infection (Dong et al, 2018). It was also previously described that influenza-affected individuals require gd T cells for effective immunity and maintenance of lung homeostasis (Xi-zhi et al, 2018;Sabbaghi et al, 2020). gd T cell exhaustion results in impaired host defense to lung infections by different pathogens like Klebsiella pneumonia, Streptococcus pneumoniae, and Staphylococcus aureus (Moore et al, 2000;Kirby et al, 2007;Cho et al, 2010).…”