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The Lung Immune Response to Nontypeable Haemophilus influenzae (Lung Immunity to NTHi).

King PT, Sharma R - J Immunol Res (2015)

Bottom Line: NTHi is present as part of the normal microbiome in the nasopharynx, from where it may spread down to the lower respiratory tract.In this context it is no longer a commensal and becomes an important respiratory pathogen associated with a range of common conditions including bronchitis, bronchiectasis, pneumonia, and particularly chronic obstructive pulmonary disease.This results in recurrent/persistent infection and chronic inflammation with consequent lung pathology.

View Article: PubMed Central - PubMed

Affiliation: Monash Lung and Sleep, Monash Medical Centre, Melbourne, VIC 3168, Australia ; Monash University Department of Medicine, Monash Medical Centre, Melbourne, VIC 3168, Australia.

ABSTRACT
Haemophilus influenzae is divided into typeable or nontypeable strains based on the presence or absence of a polysaccharide capsule. The typeable strains (such as type b) are an important cause of systemic infection, whilst the nontypeable strains (designated as NTHi) are predominantly respiratory mucosal pathogens. NTHi is present as part of the normal microbiome in the nasopharynx, from where it may spread down to the lower respiratory tract. In this context it is no longer a commensal and becomes an important respiratory pathogen associated with a range of common conditions including bronchitis, bronchiectasis, pneumonia, and particularly chronic obstructive pulmonary disease. NTHi induces a strong inflammatory response in the respiratory tract with activation of immune responses, which often fail to clear the bacteria from the lung. This results in recurrent/persistent infection and chronic inflammation with consequent lung pathology. This review will summarise the current literature about the lung immune response to nontypeable Haemophilus influenzae, a topic that has important implications for patient management.

No MeSH data available.


Related in: MedlinePlus

Factors associated with impaired macrophage immune responses to NTHi. There are some important factors that inhibit the lung macrophage response to NTHi infection. Macrophage activation through TLR4 and 2 is impaired in patients with chronic obstructive pulmonary disease (COPD) and by smoking. Phagocytosis is reduced in patients with COPD; smoking also inhibits this process as well as bacterial clearance. Macrophage effector function with cytokine production is impaired in subjects with COPD and by rhinovirus (RV) coinfection.
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fig2: Factors associated with impaired macrophage immune responses to NTHi. There are some important factors that inhibit the lung macrophage response to NTHi infection. Macrophage activation through TLR4 and 2 is impaired in patients with chronic obstructive pulmonary disease (COPD) and by smoking. Phagocytosis is reduced in patients with COPD; smoking also inhibits this process as well as bacterial clearance. Macrophage effector function with cytokine production is impaired in subjects with COPD and by rhinovirus (RV) coinfection.

Mentions: There are a number of studies that have assessed macrophage function in response to NTHi, with an emphasis on defective phagocytosis. Berenson et al. have shown that alveolar macrophages from COPD had impaired phagocytosis of radioactive labelled NTHi when compared to controls; in contrast there was no difference in results between groups in blood-derived macrophages [70]. Another study, which used a different method of fluorescently-labelled bacteria, found that macrophages from both the lung and peripheral blood of subjects with COPD had impaired phagocytosis of NTHi and S. pneumoniae [71]. There are a number of different ways that a bacterium can enter a phagocyte and the mechanisms of the impairment of phagocytosis in COPD noted in these two studies remain to be defined. A follow-up study has described that activation of nuclear erythroid-related factor 2 improves phagocytosis of NTHi by alveolar macrophages [72]. Berenson et al. have described that impairment of phagocytosis of NTHi and Moxarella catarrhalis is related to the severity of disease in COPD and is complement independent [73]. The macrophage has a number of strategies to kill phagocytosed pathogens and these include the production of reactive oxygen and nitrogen species, myeloperoxidase, the formation of the phagolysosome, and antimicrobial peptides such as defensins. There is a lack of literature about these important mechanisms in reference to NTHi infection, which have implications for both ability to clear bacteria and excessive production, contributing to local tissue damage. We have recently described that NTHi induces widespread ROS production by a variety of lung cells particularly macrophages and this increases over time with extracellular expression and this may be an important factor in the development of lung oxidative stress [74]. In addition, macrophages also produce mediators such as cytokines as part of their effector function; one study has described that there is impaired human alveolar macrophage function to NTHi antigens with decreased production of IL-8, TNF-α, and IL-1β [75]. Some key features of macrophage function in relation to NTHi infection are highlighted in Figure 2.


The Lung Immune Response to Nontypeable Haemophilus influenzae (Lung Immunity to NTHi).

King PT, Sharma R - J Immunol Res (2015)

Factors associated with impaired macrophage immune responses to NTHi. There are some important factors that inhibit the lung macrophage response to NTHi infection. Macrophage activation through TLR4 and 2 is impaired in patients with chronic obstructive pulmonary disease (COPD) and by smoking. Phagocytosis is reduced in patients with COPD; smoking also inhibits this process as well as bacterial clearance. Macrophage effector function with cytokine production is impaired in subjects with COPD and by rhinovirus (RV) coinfection.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4465770&req=5

fig2: Factors associated with impaired macrophage immune responses to NTHi. There are some important factors that inhibit the lung macrophage response to NTHi infection. Macrophage activation through TLR4 and 2 is impaired in patients with chronic obstructive pulmonary disease (COPD) and by smoking. Phagocytosis is reduced in patients with COPD; smoking also inhibits this process as well as bacterial clearance. Macrophage effector function with cytokine production is impaired in subjects with COPD and by rhinovirus (RV) coinfection.
Mentions: There are a number of studies that have assessed macrophage function in response to NTHi, with an emphasis on defective phagocytosis. Berenson et al. have shown that alveolar macrophages from COPD had impaired phagocytosis of radioactive labelled NTHi when compared to controls; in contrast there was no difference in results between groups in blood-derived macrophages [70]. Another study, which used a different method of fluorescently-labelled bacteria, found that macrophages from both the lung and peripheral blood of subjects with COPD had impaired phagocytosis of NTHi and S. pneumoniae [71]. There are a number of different ways that a bacterium can enter a phagocyte and the mechanisms of the impairment of phagocytosis in COPD noted in these two studies remain to be defined. A follow-up study has described that activation of nuclear erythroid-related factor 2 improves phagocytosis of NTHi by alveolar macrophages [72]. Berenson et al. have described that impairment of phagocytosis of NTHi and Moxarella catarrhalis is related to the severity of disease in COPD and is complement independent [73]. The macrophage has a number of strategies to kill phagocytosed pathogens and these include the production of reactive oxygen and nitrogen species, myeloperoxidase, the formation of the phagolysosome, and antimicrobial peptides such as defensins. There is a lack of literature about these important mechanisms in reference to NTHi infection, which have implications for both ability to clear bacteria and excessive production, contributing to local tissue damage. We have recently described that NTHi induces widespread ROS production by a variety of lung cells particularly macrophages and this increases over time with extracellular expression and this may be an important factor in the development of lung oxidative stress [74]. In addition, macrophages also produce mediators such as cytokines as part of their effector function; one study has described that there is impaired human alveolar macrophage function to NTHi antigens with decreased production of IL-8, TNF-α, and IL-1β [75]. Some key features of macrophage function in relation to NTHi infection are highlighted in Figure 2.

Bottom Line: NTHi is present as part of the normal microbiome in the nasopharynx, from where it may spread down to the lower respiratory tract.In this context it is no longer a commensal and becomes an important respiratory pathogen associated with a range of common conditions including bronchitis, bronchiectasis, pneumonia, and particularly chronic obstructive pulmonary disease.This results in recurrent/persistent infection and chronic inflammation with consequent lung pathology.

View Article: PubMed Central - PubMed

Affiliation: Monash Lung and Sleep, Monash Medical Centre, Melbourne, VIC 3168, Australia ; Monash University Department of Medicine, Monash Medical Centre, Melbourne, VIC 3168, Australia.

ABSTRACT
Haemophilus influenzae is divided into typeable or nontypeable strains based on the presence or absence of a polysaccharide capsule. The typeable strains (such as type b) are an important cause of systemic infection, whilst the nontypeable strains (designated as NTHi) are predominantly respiratory mucosal pathogens. NTHi is present as part of the normal microbiome in the nasopharynx, from where it may spread down to the lower respiratory tract. In this context it is no longer a commensal and becomes an important respiratory pathogen associated with a range of common conditions including bronchitis, bronchiectasis, pneumonia, and particularly chronic obstructive pulmonary disease. NTHi induces a strong inflammatory response in the respiratory tract with activation of immune responses, which often fail to clear the bacteria from the lung. This results in recurrent/persistent infection and chronic inflammation with consequent lung pathology. This review will summarise the current literature about the lung immune response to nontypeable Haemophilus influenzae, a topic that has important implications for patient management.

No MeSH data available.


Related in: MedlinePlus