The Human Immune Response to Respiratory Syncytial Virus Infection

Abstract

Respiratory syncytial virus (RSV) is an important etiological agent of respiratory infections, particularly in children. Much information regarding the immune response to RSV comes from animal models and studies. Here, we provide a comprehensive description of the human immune response to RSV infection, based on a systematic literature review of research on infected humans. There is an initial strong neutrophil response to RSV infection in humans, which is positively correlated with disease severity and mediated by interleukin-8 (IL-8). Dendritic cells migrate to the lungs as the primary antigen-presenting cell. An initial systemic T-cell lymphopenia is followed by a pulmonary CD8 T-cell response, mediating viral clearance. Humoral immunity to reinfection is incomplete, but RSV IgG and IgA are protective. B-cell-stimulating factors derived from airway epithelium play a major role in protective antibody generation. Gamma interferon (IFN-γ) has a strongly protective role, and a Th2-biased response may be deleterious. Other cytokines (particularly IL-17A), chemokines (particularly CCL-5 and CCL-3), and local innate immune factors (including cathelicidins and IFN-λ) contribute to pathogenesis. In summary, neutrophilic inflammation is incriminated as a harmful response, whereas CD8 T cells and IFN-γ have protective roles. These may represent important therapeutic targets to modulate the immunopathogenesis of RSV infection.

Association of Dynamic Changes in the CD4 T-Cell Transcriptome With Disease Severity During Primary Respiratory Syncytial Virus Infection in Young Infants

“…Most studies investigating RSV disease pathogenesis have measured the presence and levels of various inflammatory proteins, such as cytokines and chemokines in blood or respiratory secretions, or their in vitro production by peripheral blood mononuclear cells, often with disparate results [9,[11][12][13][14][15]. Most studies investigating RSV disease pathogenesis have measured the presence and levels of various inflammatory proteins, such as cytokines and chemokines in blood or respiratory secretions, or their in vitro production by peripheral blood mononuclear cells, often with disparate results [9,[11][12][13][14][15].…”

“…Host immune responses are also thought to influence disease manifestations, including severity [6][7][8][9]. Experimental animal models of RSV infection suggest that Th2 CD4 immune-dominant responses, as well as diminished or impaired anti-inflammatory T-regulatory (Treg) cell function and increased Th17 responses, contribute to increased lung pathology [6,7,10].…”

“…Experimental animal models of RSV infection suggest that Th2 CD4 immune-dominant responses, as well as diminished or impaired anti-inflammatory T-regulatory (Treg) cell function and increased Th17 responses, contribute to increased lung pathology [6,7,10]. Data from infant studies are less compelling, with some supporting and others refuting that a T2-dominant response is responsible for severe disease [9,[11][12][13][14][15].…”

Impaired tumor necrosis factor‐α secretion by CD4 T cells during respiratory syncytial virus bronchiolitis associated with recurrent wheeze

“…Our finding is consistent with the study by Turi et al evaluating nasal immune response phenotypes in infants with RSV infection in which they demonstrated low non‐IFN antiviral immune response, including TNF‐α, as significantly associated with recurrent wheezing in the first and second‐year following RSV infection. In the upper airways, a decrease in IL‐10 potentiates an increase in the TNF‐α response which controls the viral infection . As diminished TNF‐α observed in recurrent wheezers after both stimulation conditions from peripheral blood‐derived CD4+ T cells and the significant differences in the levels of TNF‐α among four wheezing categories, evidence suggests that (a) CD4+ T cells may be impaired in their production of TNF‐α during RSV infection and (b) TNF‐α may play roles in the pathogenesis of airway inflammation and subsequent wheezing following severe RSV bronchiolitis in children.…”

Стан Місцевого Захисту Та Особливості Мікробної Колонізації Слизових Оболонок Верхніх Дихальних Шляхів У Дітей Із Бактеріальними Ускладненнями ГРВІ

“…Так, доведено, що мікробіотичний профіль дихальних шляхів у ранньому дитинстві асоційований з ризиком, частотою та тяжкістю ін-фекційної респіраторної патології в подальшому житті; рання взаємодія інфекційних агентів, напри-клад вірусів, з респіраторною мікробіотою модулює імунну відповідь дитини, що потенційно впливає на перебіг респіраторних захворювань і майбутнє респіраторне здоров'я дитини [6]. Респіраторна мі-кробіота розглядається як «воротар», що забезпечує резистентність до колонізації патогенами, включе-на у процеси дозрівання та підтримання гомеостазу респіраторної фізіології та імунітету [9][10][11]. Отже, на наш погляд, найбільш цікавим для дослідження є кластер локальних імунологічних факторів.…”