Insights on persistent airway infection by non-typeable Haemophilus influenzae in chronic obstructive pulmonary disease

Abstract

Non-typeable Haemophilus influenzae (NTHi) is the most common bacterial cause of infection of the lower airways in adults with chronic obstructive pulmonary disease (COPD). Infection of the COPD airways causes acute exacerbations, resulting in substantial morbidity and mortality. NTHi has evolved multiple mechanisms to establish infection in the hostile environment of the COPD airways, allowing the pathogen to persist in the airways for months to years. Persistent infection of the COPD airways contributes to chronic airway inflammation that increases symptoms and accelerates the progressive loss of pulmonary function, which is a hallmark of the disease. Persistence mechanisms of NTHi include the expression of multiple redundant adhesins that mediate binding to host cellular and extracellular matrix components. NTHi evades host immune recognition and clearance by invading host epithelial cells, forming biofilms, altering gene expression and displaying surface antigenic variation. NTHi also binds host serum factors that confer serum resistance. Here we discuss the burden of COPD and the role of NTHi infections in the course of the disease. We provide an overview of NTHi mechanisms of persistence that allow the pathogen to establish a niche in the hostile COPD airways.

Interaction with the host: the role of fibronectin and extracellular matrix proteins in the adhesion of Gram-negative bacteria

“…The presence of a polysaccharide capsule classifies H. influenzae in encapsulated strains responsible for invasive disease and unencapsulated (nontypeable NTHi) strains found in mucosal infections in the upper and lower respiratory tract [146]. H. influenzae prefers binding to non-ciliated cells, areas with damaged epithelium and mucus present in the respiratory tract [147] via a number of OMPs that influence the process of adherence and colonization [148].…”

In Vitro Anti-NTHi Activity of Haemophilin-Producing Strains of Haemophilus haemolyticus

“…Similarly, an isogenic mutant of two heme acquisition pathways was unable to sustain bacteraemia or produce meningitis in a rat model of invasive disease [18]. Thus, heme acquisition pathways represent potentially high value targets for the development of novel therapies for the eradication of NTHi from the respiratory tract [19,20].…”

Moonlighting of Haemophilus influenzae heme acquisition systems contributes to the host airway-pathogen interplay in a coordinated manner

“…Nontypeable Haemophilus influenzae (NTHi) is typically a commensal of the human upper airways, but also a common opportunistic pathogen in the lower airways of patients with COPD [31][32][33][34][35]. NTHi persistence within the COPD lungs contributes to airway inflammation that results in worsening of symptoms and promotes disease progression [33,[36][37][38].…”