Reshaping Our Knowledge: Advancements in Understanding the Immune Response to Human Respiratory Syncytial Virus

Abstract

Human respiratory syncytial virus (hRSV) is a significant cause of respiratory tract infections, particularly in young children and older adults. In this review, we aimed to comprehensively summarize what is known about the immune response to hRSV infection. We described the innate and adaptive immune components involved, including the recognition of RSV, the inflammatory response, the role of natural killer (NK) cells, antigen presentation, T cell response, and antibody production. Understanding the complex immune response to hRSV infection is crucial for developing effective interventions against this significant respiratory pathogen. Further investigations into the immune memory generated by hRSV infection and the development of strategies to enhance immune responses may hold promise for the prevention and management of hRSV-associated diseases.

Keywords: RSV; immune response; prevention strategy; syncytial respiratory virus.

Figure 1

(A) Virus entry into the host cell: the adhesion to the cell membrane of the ciliate cells of the respiratory epithelium is mediated by the interaction between F and G proteins and some membrane receptors such as TLR4, CXCR1, and nucleolin. (B) HRSV molecular structure. Create in BioRender.com. (accessed on 14 August 2023).

Figure 2

Global burden of RSV infection disease among children population from 0 to 60 months (A,B) [4]. Burden of RSV infection disease in high-income countries among adults with comorbidity (C), and elders (D) [8,9]. Create in BioRender.com. (accessed on 14 August 2023).

Figure 3

Innate and adaptive immune response to hRSV infection, inspired and modified from reference [21]. Graphic: The peak of the viral load and the severity of clinical manifestations is expected between the second and the fourth day after the onset of symptoms. A similar trend, with a 2–3 day delay, is typical of the blood neutrophils precursors. CD8 T cells peaked between the 11th and 14th days [70]. (1) Cellular infection triggers the release of early inflammatory mediators (e.g., IFNs, TNF-α, and chemokines), which recruit natural killer (NK) cells and polymorphonuclear leukocytes (PMNs) that have the ability to kill the infected cells, thus limiting viral replication but contribute to tissue damage. (2) Dendritic cells carry viral antigens to regional lymph nodes. Presentation of viral antigens to CD4⁺ T-lymphocytes occurs, and primed T-cells activate B-lymphocytes and CD8⁺ T-cells. They all migrate back to the infected epithelium with the further release of mediators and recruitment of additional inflammatory cells, including PMNs and mononuclear cells. (3) CD4-Th1 response and CD8 cytotoxic activity contribute to viral clearance. (4) Antibodies are produced by both T-cell-independent and T-cell-mediated B lymphocyte activation. Create in BioRender.com. (accessed on 14 August 2023).