Interrupting the Conversation: Implications for Crosstalk Between Viral and Bacterial Infections in the Asthmatic Airway

Abstract

Asthma is a heterogeneous, chronic respiratory disease affecting 300 million people and is thought to be driven by different inflammatory endotypes influenced by a myriad of genetic and environmental factors. The complexity of asthma has rendered it challenging to develop preventative and disease modifying therapies and it remains an unmet clinical need. Whilst many factors have been implicated in asthma pathogenesis and exacerbations, evidence indicates a prominent role for respiratory viruses. However, advances in culture-independent detection methods and extensive microbial profiling of the lung, have also demonstrated a role for respiratory bacteria in asthma. In particular, airway colonization by the Proteobacteria species Nontypeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) is associated with increased risk of developing recurrent wheeze and asthma in early life, poor clinical outcomes in established adult asthma and the development of more severe inflammatory phenotypes. Furthermore, emerging evidence indicates that bacterial-viral interactions may influence exacerbation risk and disease severity, highlighting the need to consider the impact chronic airway colonization by respiratory bacteria has on influencing host responses to viral infection. In this review, we first outline the currently understood role of viral and bacterial infections in precipitating asthma exacerbations and discuss the underappreciated potential impact of bacteria-virus crosstalk in modulating host responses. We discuss the mechanisms by which early life infection may predispose to asthma development. Finally, we consider how infection and persistent airway colonization may drive different asthma phenotypes, with a view to identifying pathophysiological mechanisms that may prove tractable to new treatment modalities.

Nontypeable Haemophilus influenzae infection of pulmonary macrophages drives neutrophilic inflammation in severe asthma

“…As our work suggests that NTHi‐infected macrophages may be the source of IL‐1β‐induced inflammation in the asthmatic airway, stratifying patients based on NTHi presence may result in better therapeutic outcomes. IL‐1 pathway interventions have yet to be shown to be successful in asthma, and may only be effective in certain patient cohorts, such as those colonized with NTHi 57 …”

Moraxella occupied the largest proportion in the nasal microbiome in healthy children, which potential protect them from COVID-19

“…Metagenomic analysis of RNA sequencing data showed a significant decrease in commensal bacteria as the number of days of COVID-19 infection increased [ 22 ].There have been reported that Moraxella as a core genus of nasal commensal bacteria in children [ 23 , 24 ], and this is in line with our findings. In addition, Moraxella can affect the immune system of the respiratory tract [ 25 ]. Sönnerborg A et al demonstrated that Moraxella correlated inversely to inflammation marker CRP and D-dimer [ 26 ].…”

Impact of Therapeutics on Unified Immunity During Allergic Asthma and Respiratory Infections

“…The knowledge of the relationship between bacteria and asthma continue to grow rapidly, in part due to the utilization of new technologies for bacterial identification, particularly 16S ribosomal RNA gene sequencing ( 92 ). Appreciation of the human microbiome, especially the lung microbiome [considered sterile until recently ( 93 )], allowed researchers to recognize the impact of specific bacteria in different pulmonary disorders ( 94 ) and their interactions with viral infections in the context of asthma ( 95 ). In the following section we discuss the participation of the most significant bacteria linked to asthma ( Figure 1 ).…”

“…Both neutrophilic and eosinophilic inflammation can result after Mcat infection ( 95 ). In patients with neutrophilic asthma, high abundance of Moraxella and Haemophilus taxa have been identified in sputum samples ( 126 , 127 ).…”