Th17 Lymphocytes in Respiratory Syncytial Virus Infection

Abstract

Infection by respiratory syncytial virus (RSV) affects approximately 33 million infants annually worldwide and is a major cause of hospitalizations. Helper T lymphocytes (Th) play a central role in the immune response during such infections. However, Th lymphocytes that produce interleukin 17 (IL-17), known as Th17 lymphocytes, in addition to been protective can also cause pathology that accompany this type of infection. The protective effects of Th17 is associated with better prognosis in most infected individuals but heightened Th17 responses causes inflammation and pathology in others. Studies employing animal models haves shown that activated Th17 lymphocytes recruit neutrophils and facilitate tertiary lymphoid structure development in infected lungs. However, IL-17 also inhibits the ability of CD8+ lymphocytes to clear viral particles and acts synergistically with the innate immune system to exacerbate inflammation. Furthermore, IL-17 enhances IL-13 production which, in turn, promotes the activation of Th2 lymphocytes and excessive mucus production. Studies of these animal models have also shown that a lack of, or inadequate, responses by the Th1 subset of T lymphocytes enhances Th17-mediated responses and that this is detrimental during RSV co-infection in experimental asthma. The available evidence, therefore, indicates that Th17 can play contradictory roles during RSV infections. The factors that determine the shift in the balance between beneficial and adverse Th17 mediated effects during RSV infection remains to be determined.

The role of Th17 and Treg responses in the pathogenesis of RSV infection

“…In contrast, IL-17 has no direct effect on airway hyper-responsiveness, which is solely Th2-mediated (50). In this context, a number of studies showed that RSVinfected mice simultaneously produced IL-17 and IL-13 suggesting that the Th17 response is concomitant with the Th2 response (50,55,56). Thirdly, IL-17 has been associated with increased neutrophilic infiltration in the lungs.…”

“…Firstly, IL-17 will cause exaggerated mucus production (50,55). Secondly, IL-17 is thought to enhance Th2 cytokine production in a Th2 skewed environment (50).…”

“…This effect is brought forth by enhancing the production of CXC chemokines by stromal cells, such as IL-8 (50). Fourthly, IL-17 seems to diminish effector CD8 + T-cell responses through negative regulation of T-bet and Eomes, two transcription factors that regulate the CD8 + cytotoxic T-cell effector functions, thus diminishing viral clearance (50,55).…”

“…Although evidence is less conclusive than is the case for the Treg immune response, the Th17 immune response is thought to hamper an efficient viral clearance and further enhance a Th2 immune response resulting in a more severe clinical picture (50). Moreover, the CD8 + T cellular response during RSV infection seems to be counteracted by Th17 cells through IL-17 while being stimulated by Treg cells through promoting early influx of CD8 + T-cells to the lungs, therefore resulting in efficient viral clearance (37,50,55). It is also important to note the opposing effect of IL-10, i.e., inhibitory on Th17 cells and stimulatory on Treg cells (41,74).…”

Host and Viral Factors in Respiratory Syncytial Virus Infection

“…However, this may be an overly simplistic approach, as a recent study in mice has reported that shifting the host immune response toward T h 1 actually decreases the production of RSV-neutralizing antibodies, which would have the effect of limiting the effectiveness of a vaccine [90 • ]. In addition to T h 1 and T h 2 lymphocytes, the subpopulation of T h 17 lymphocytes has been implicated in RSV infection, further adding to the complexity of the host immune response [91].…”