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T cells are a critical component of the immune system and required for protection against viral and bacterial infections. However, the capacity of these cells to provide sufficient protection declines with age, leading to an increased susceptibility to and mortality from infection in older individuals. In many cases, it also contributes to poor vaccine-induced immunity. Understanding the basic biology behind T cell aging is key to unraveling these defects and, in turn, designing more effective vaccines and therapeutics for the older population. Here, we will discuss recent studies that have provided significant insight into the features of T cell aging, how these features may contribute to poor immune responses with advancing age and newer avenues of research that may further enhance anti-viral immunity in older individuals.

Significant advances have been made recent years elucidating antiviral immune mechanisms that protect the host from viral infection. Similarly, our understanding of how viruses bind, enter, and replicate within host cells has continued to grow. Yet, viruses continue to take a toll on human health. The influence of chemicals in the environment is among key factors that influence outcomes of viral infection. There is a growing appreciation of the effects that exogenous environmental chemical exposures have on the immune system and antiviral immunity. Epidemiological studies have linked a variety of chemical exposures to poorer health, increased incidence of infection, and worsened vaccine responses. However, the mechanisms that govern these associations are not well understood, limiting our ability to predict or mitigate the effects of environmental exposures on public health. This brief review focuses on recent advances in the field, highlighting novel in vitro and in vivo findings informed by past foundational studies. Furthermore, current information suggests avenues of investigation that have yet to be explored, but which will significantly impact on our understanding about how environmental exposures impact viral defenses, vaccine efficacy, and the spread of contemporary and emerging viral pathogens.

The cellular response to dsRNA or its synthetic analog polyinosinic–polycytidylic acid (poly I:C) results in IRF-3-, IRF-7- and NF-kB-mediated activation of type 1 IFNs and pro-inflammatory cytokines critical for innate antiviral immune responses. To investigate whether cigarette smoke compromises type 1 IFN signaling in humans, peripheral blood mononuclear cells (PBMCs) from non-smoking individuals were treated with smoke-conditioned media (SCM) and stimulated with poly I:C. We observed a marked attenuation of IRF-3 and NF-kB activation in PBMCs exposed to SCM compared to control PBMCs. Similarly, PBMCs from smokers or splenocytes from smoke-exposed mice also displayed marked reduction of poly I:C-induced antiviral responses compared with either non-smokers or sham-exposed mice. Cigarette smoke was found to block the production of type I IFNs following poly I:C treatment and inhibit subsequent STAT1 activation. Finally, we confirmed that inhibition of IFN-β, but not IFN-α, predominantly contributes to the cigarette smoke-mediated suppression of innate antiviral responses. These findings provide novel mechanistic insights to the susceptibility of cigarette smokers to viral infections.