Respiratory virus-induced heterologous immunity: Part of the problem or part of the solution?

Purpose: To provide current knowledge on respiratory virus-induced heterologous immunity (HI) with a focus on humoral and cellular cross-reactivity. Adaptive heterologous immune responses have broad implications on infection, autoimmunity, allergy and transplant immunology. A better understanding of the mechanisms involved might ultimately open up possibilities for disease prevention, for example by vaccination.

Methods: A structured literature search was performed using Medline and PubMed to provide an overview of the current knowledge on respiratory-virus induced adaptive HI.

Results: In HI the immune response towards one antigen results in an alteration of the immune response towards a second antigen. We provide an overview of respiratory virus-induced HI, including viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), coronavirus (CoV) and influenza virus (IV). We discuss T cell receptor (TCR) and humoral cross-reactivity as mechanisms of HI involving those respiratory viruses. Topics covered include HI between respiratory viruses as well as between respiratory viruses and other pathogens. Newly developed vaccines, which have the potential to provide protection against multiple virus strains are also discussed. Furthermore, respiratory viruses have been implicated in the development of autoimmune diseases, such as narcolepsy, Guillain-Barré syndrome, type 1 diabetes or myocarditis. Finally, we discuss the role of respiratory viruses in asthma and the hygiene hypothesis, and review our recent findings on HI between IV and allergens, which leads to protection from experimental asthma.

Conclusion: Respiratory-virus induced HI may have protective but also detrimental effects on the host. Respiratory viral infections contribute to asthma or autoimmune disease development, but on the other hand, a lack of microbial encounter is associated with an increasing number of allergic as well as autoimmune diseases. Future research might help identify the elements which determine a protective or detrimental outcome in HI-based mechanisms.