The changing face of asthma and its relation with microbes

Abstract

During the past 50 years, the prevalence of asthma has increased and this has coincided with our changing relation with microorganisms. Asthma is a complex disease associated with local tissue inflammation of the airway that is determined by environmental, immunological, and host genetic factors. In a subgroup of sufferers, respiratory infections are associated with the development of chronic disease and more frequent inflammatory exacerbations. Recent studies suggest that these infections are polymicrobial in nature. Furthermore, there is increasing evidence that the recently discovered asthma airway microbiota may play a critical role in pathophysiological processes associated with the disease. Here, we discuss the current data regarding a possible role for infection in chronic asthma with a particular focus on the role bacteria may play. We discuss recent advances that are beginning to elucidate the complex relations between the microbiota and the immune response in asthma patients. We also highlight the clinical implications of these recent findings in regards to the development of novel therapeutic strategies.

Keywords: airway; allergens; asthma; infection; inflammation; microbiota.

Figure 1

Microorganisms involved in asthma airway colonization. A cross-section of the human lower respiratory tract is depicted, showing sites of infection for different microorganisms and the effects that they have on airway function. The phylogenetic ring depicts the percentage abundance of bacterial phyla identified in various biological samples taken from the airways of asthma patients (Information used to compile figure was reported in , . Inner ring (bronchoscopic brushing samples); middle ring (BAL samples), and outer ring (induced sputum samples). Abbreviation: BAL, bronchoalveolar lavage.

Figure 2

Bacterial and viral infections of the airways activate immune and structural cells, promoting inflammation and influencing responses to other pathogens, allergens and pollution. The schematic depicts potential triggers and innate immune response of eosinophilic (Th2 dependent) and neutrophlic (non-Th2 dependent) asthma. Left panel: Environmental allergens such as pollen and mold spores can trigger Th2 asthma. Th2 immune processes begin with the development of Th2 cells and their production of the cytokines IL-4, IL-5, and IL-13. These cytokines stimulate allergic and eosinophilic inflammation as well as epithelial and smooth-muscle changes that contribute to asthma pathobiology. Right panel: Cigarette smoke, pollutants and the PAMPs from airway microbes including LPS from bacteria or ssRNA from respiratory viruses can potentially trigger non-Th2 asthma. There is a range of factors that can contribute to the development of non-Th2 asthma. These factors include infection-related elements, Th1 and Th17 immunity, non-Th2 associated smooth-muscle changes and the development of neutrophlic inflammation. Abbreviations: APC, antigen-presenting cell; CRTH2, chemoattractant receptor-homologous molecule expressed on Th2 cells; dsRNA, double-stranded RNA; PGD2, prostaglandin D2. IFN, interferon; GRO, growth-regulated oncogene; IL, interleukin; LPS, lipopolysaccharide; PAMP, pathogen associated molecular pattern; ssRNA, single-stranded RNA; Th, T helper; TLR, Toll-like receptor.