NontypeableHaemophilus influenzae: Pathogenesis and Prevention

Abstract

SUMMARY In this paper, we describe the ability of nontypeable Haemophilus influenzae (NTHi) to coexist with the human host and the devastating results associated with disruption of the delicate state of balanced pathogenesis, resulting in both acute and chronic respiratory tract infections. It has been seen that the strains of NTHi causing disease show a marked genetic and phenotypic diversity but that changes in the lipooligosaccharide (LOS) and protein size and antigenicity in chronically infected individuals indicate that individual strains of NTHi can remain and adapt themselves to avoid expulsion from their infective niche. The lack of reliance of NTHi on a single mechanism of attachment and its ability to interact with the host with rapid responses to its environment confirmed the success of this organism as both a colonizer and a pathogen. In vitro experiments on cell and organ cultures, combined with otitis media and pulmonary models in chinchillas, rats, and mice, have allowed investigations into individual interactions between NTHi and the mammalian host. The host-organism interaction appears to be a two-way process, with NTHi using cell surface structures to directly interact with the mammalian host and using secreted proteins and LOS to change the mammalian host in order to pave the way for colonization and invasion. Many experiments have also noted that immune system evasion through antigenic variation, secretion of enzymes and epithelial cell invasion allowed NTHi to survive for longer periods despite a specific immune response being mounted to infection. Several outer membrane proteins and LOS derivatives are discussed in relation to their efficacy in preventing pulmonary infections and otitis media in animals. General host responses with respect to age, genetic makeup, and vaccine delivery routes are considered, and a mucosal vaccine strategy is suggested.

The variable P5 proteins of typeable and non‐typeable Haemophilus influenzae target human CEACAM1

“…The protein P5 has received considerable attention as a potential vaccine candidate and is implicated in colonization and pathogenesis (Foxwell et al, 1998). Synthetic P5 peptides appear to be protective in animal models of infection, but the mechanisms involved are unclear (Webb and Cripps, 2000).…”

Mutational analysis of human CEACAM1: the potential of receptor polymorphism in increasing host susceptibility to bacterial infection

“…Non-typable Hi (NTHi), which lack a polysaccharide capsule, are associated with localized respiratory tract and conjunctival infections (Foxwell et al, 1998). Strains belonging to Hi-biogroup aegyptius (Hi-aeg) are also associated with Brazilian purpuric fever (Foxwell et al, 1998). The factors that determine susceptibility to infection by these frequent colonizers are not entirely clear.…”

Chronic bronchial infection in COPD. Is there an infective phenotype?

“…Additionally, some microorganisms are able to invade and survive within airway epithelial cells and macrophages. 43,44 With the use of in situ hybridisation and immunofluorescence microscopy for the detection of intracellular NTHi in bronchial biopsies, this microorganism was found in 33% and 87% of stable and severely exacerbated chronic bronchitis patients, respectively, but not in healthy adults. 24 The most frequently identified risk factors for colonisation with PPMs are current or previous smoking, 25,30,31 impaired lung function defined by a reduction in FEV 1 and/or forced vital capacity (FVC), 2,30,31 comorbid conditions, 25 increased rate of previous exacerbations 25,39 and the presence of bronchiectasis.…”

“…This interaction is best described for NTHi and involves adherence to mucous membranes and extracellular matrix, damage to epithelial cells, ciliotoxic activity, an increase in mucin production, as well as complex mechanisms of evading host immune defences such as invasion into the epithelial cells, production of IgA proteases and antigenic heterogeneity. 44,45 Some host factors such as reduced mucociliary clearance, mucus hypersecretion and bronchiectasis are also involved, 26 although it is not always clear whether some these features are really risk factors for acquiring bacteria or their consequence. Recent findings have stressed the role of innate immunity impairment in COPD, which among others, may manifest as defective phagocytosis and hyporesponsiveness of alveolar macrophages to bacterial antigens, leading to reduced clearance of bacterial pathogens and subsequent predisposition to colonisation and infection.…”