The Infectious March: The Complex Interaction Between Microbes and the Immune System in Asthma

Abstract

There has been significant progress in our knowledge about the relationship between infectious disease and the immune system in relation to asthma, but many unanswered questions still remain. Respiratory tract infections such as those caused by respiratory syncytial virus and rhinovirus during the first two years of life are still clearly associated with later wheezing and asthma, but the mechanism has not been completely worked out. Is there an 'infectious march' triggered by infection in infancy that progresses to disease pathology or are infants who contract respiratory infections predisposed to developing asthma? This review focuses on the common themes in the interaction between microbes and the immune system and presents a critical appraisal of the evidence to date. The various mechanisms whereby microbes alter the immune response and how this might influence asthma are discussed along with new and promising clinical practices for prevention and therapy. Recent advances in utilizing sensitive PCR detection methods have allowed more rigorous testing of the causality hypothesis of virus infection leading to asthma, but the evidence is still equivocal. Various exceptions and inconsistencies in the clinical trials are discussed in light of new guidelines for subject inclusion/exclusion in hopes of providing some standardization. In spite of past failures in vaccination and disappointing results of some clinical trials, the new strategies for prophylaxis including RNA interference and targeted delivery of microbicides offer a large dose of hope to a world suffering from an increasing incidence of asthma and a huge burden of healthcare cost and loss of quality of life.

Rhinovirus-Infected Epithelial Cells Produce More IL-8 and RANTES Compared With Other Respiratory Viruses

“…Neutrophil recruitment was correlated with virus-mediated influx of IL-8 in both asthmatic and non-atopic individuals 4. In the case of RSV infection, neutrophils are also abundant in the nasal lavages of RSV-infected adults and infants,21 and early cytokines and chemokines such as IL-12, IL-18, MIP-1a, IL-8, and RANTES are upregulated in the upper respiratory tract 22. These studies provide evidence that the infiltrating cell and chemokine profiles of both viruses are similar in virus-infected murine models and human subjects.…”