Related Experiment Videos
The pathogenesis of disease due to nontypeable Haemophilus influenzae
Gail G Hardy1, Simone M Tudor, Joseph W St Geme
1Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
Abstract:
To summarize, the pathogenesis of disease due to nontypeable H. influenzae involves multiple steps and the interplay of a number of bacterial and host factors, as shown in Fig. 1. Following entry into the upper respiratory tract, bacteria encounter the mucociliary escalator. The P2 and P5 outer-membrane proteins and probably other factors promote bacterial binding to mucus, and elaboration of LOS causes damage to ciliated cells and impairs mucociliary function. Subsequently, several adhesins, including HMW1 and HMW2, pili, Hia, Hap, and others, mediate direct adherence to nonciliated epithelial cells. Cleavage of IgA1, invasion into cells and the subepithelial space, and phase and antigenic variation facilitate evasion of local immune mechanisms. Binding and uptake of iron and heme allow organisms to persist on the respiratory mucosa despite the relative scarcity of these nutrients. In the setting of a viral infection, allergic disease, or exposure to cigarette smoke, bacteria spread from the nasopharynx to other sites within the respiratory tract and produce symptomatic disease.
Insights
Nontypeable Haemophilus influenzae pathogenesis involves bacterial factors like adhesins and outer-membrane proteins that damage host cells and evade immunity. Host factors like viral infections or smoke exposure promote disease spread.
Area of Science:
- Microbiology
- Immunology
- Pathogenesis
Background:
- Nontypeable Haemophilus influenzae (NTHi) causes respiratory tract infections.
- Understanding NTHi pathogenesis is crucial for developing effective treatments.
Purpose of the Study:
- To elucidate the multifaceted pathogenesis of NTHi infections.
- To identify key bacterial and host factors involved in NTHi disease.
Main Methods:
- Review of bacterial adherence mechanisms.
- Analysis of host-pathogen interactions.
- Examination of immune evasion strategies.
Main Results:
- NTHi utilizes outer-membrane proteins (P2, P5) and LOS for initial mucus binding and ciliated cell damage.
- Adhesins (HMW1, HMW2, Hia, Hap) mediate adherence to epithelial cells.
- Mechanisms like IgA1 cleavage, invasion, and phase variation aid immune evasion.
- Iron and heme uptake facilitate NTHi persistence.
Conclusions:
- NTHi pathogenesis is a complex, multi-step process.
- Bacterial factors and host conditions (viral infections, smoke) drive disease progression.
- Targeting bacterial adherence and immune evasion could be therapeutic strategies.