The Interplay Between Immune Response and Bacterial Infection in COPD: Focus Upon Non-typeable Haemophilus influenzae

Abstract

Chronic obstructive pulmonary disease (COPD) is a debilitating respiratory disease and one of the leading causes of morbidity and mortality worldwide. It is characterized by persistent respiratory symptoms and airflow limitation due to abnormalities in the lower airway following consistent exposure to noxious particles or gases. Acute exacerbations of COPD (AECOPD) are characterized by increased cough, purulent sputum production, and dyspnea. The AECOPD is mostly associated with infection caused by common cold viruses or bacteria, or co-infections. Chronic and persistent infection by non-typeable Haemophilus influenzae (NTHi), a Gram-negative coccobacillus, contributes to almost half of the infective exacerbations caused by bacteria. This is supported by reports that NTHi is commonly isolated in the sputum from COPD patients during exacerbations. Persistent colonization of NTHi in the lower airway requires a plethora of phenotypic adaptation and virulent mechanisms that are developed over time to cope with changing environmental pressures in the airway such as host immuno-inflammatory response. Chronic inhalation of noxious irritants in COPD causes a changed balance in the lung microbiome, abnormal inflammatory response, and an impaired airway immune system. These conditions significantly provide an opportunistic platform for NTHi colonization and infection resulting in a “vicious circle.” Episodes of large inflammation as the consequences of multiple interactions between airway immune cells and NTHi, accumulatively contribute to COPD exacerbations and may result in worsening of the clinical status. In this review, we discuss in detail the interplay and crosstalk between airway immune residents and NTHi, and their effect in AECOPD for better understanding of NTHi pathogenesis in COPD patients.

Emerging Principles in Myelopoiesis at Homeostasis and during Infection and Inflammation

“…Because the myeloid system also plays a role in basically all non-communicable acute and chronic inflammatory conditions (Medzhitov, 2008), we exemplify here new findings for several of the deadliest diseases according to the Global Burden of Disease 2015 Study (Wang et al, 2016), namely myocardial infarction (MI), stroke, atherosclerosis, chronic obstructive pulmonary diseases (COPD), and cancer. Although the acute inflammatory component is most prominent in MI and stroke, atherosclerosis, COPD, or cancer are mainly characterized by a long-term chronic inflammatory response, which certainly also comes with periods of acute events, particularly in the context of superimposed infections (Su et al, 2018;Wang et al, 2018).…”

The persistence of NontypeableHaemophilus influenzaefuels airway inflammation

“…These approaches will help to better explore the contribution of NTHi persistence on disease progression, pulmonary exacerbations or super infection events, such as the "predisposition" to P. aeruginosa infection. Moreover, NTHi infections are also commonly associated with other chronic respiratory diseases with different aetiology, such as COPD [3,4,27]. Therefore, the murine model developed in this study will be exploitable to determine the contribution of the bacterial persistence and new therapeutic approaches for other lung diseases mediated by NTHi infection.…”

“…Recurrent or chronic infections by several opportunistic pathogens are common in patients affected by different chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) [1][2][3]. Infections by Nontypeable Haemophilus influenzae (NTHi), a noncapsulated Gram-negative bacterium, are associated with worse clinical prognosis in several chronic respiratory diseases, such as COPD [4,5], while its pathogenic potential in CF disease is still controversial.…”

Host responses to mucosal biofilms in the lung and gut

“…At baseline COPD airways in humans are highly inflamed, with reports of increased neutrophils, eosinophils, mast cells, dendritic cells, macrophages, and T and B lymphocytes. 79 Microbial infections, such as those induced by NTHi, can further exacerbate the inflammatory environments of COPD respiratory tissues. H. influenzae is a Gram-negative coccobacillus, and is the most common bacterium associated with COPD, colonizing 60% of COPD patients whereas P. aeruginosa only colonizes 6% of COPD patients.…”

“…H. influenzae is a Gram-negative coccobacillus, and is the most common bacterium associated with COPD, colonizing 60% of COPD patients whereas P. aeruginosa only colonizes 6% of COPD patients. 58,79 NTHi can form biofilms that are resistant to host-clearance responses, but many NTHi biofilm observations are from in vitro studies and models of infection, such as otitis media in the chinchilla. 80,81 Thus, the relevance of NTHi biofilms to COPD in vivo is still up for debate.…”