Invasive Disease Caused by Nontypeable<i>Haemophilus influenzae</i>

Langereis, Jeroen D.; Jonge, Marien I. de

doi:10.3201/eid2110.150004

Cited by 101 publications

(103 citation statements)

References 39 publications

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“…Binding of Protein H to FHL-1 was mediated via its SCR 7 (Fleury et al, 2014). NTHi strains do not express Protein H but can recruit FH via outer membrane protein P5 (OmpP5) (Rosadini et al, 2014; Langereis and de Jonge, 2015). OmpP5, a member of the OmpA protein family, is expressed in both NTHi strains as well as typable strains (Hill et al, 2001).…”

Section: Inhibiting the Ap: Fh And Fhl-1mentioning

confidence: 99%

“…OmpP5, a member of the OmpA protein family, is expressed in both NTHi strains as well as typable strains (Hill et al, 2001). Nonetheless, it is only actively involved in preventing serum killing via the AP in NTHis, most probably due to the sequence variations in OmpP5 (Hill et al, 2001; Rosadini et al, 2014; Langereis and de Jonge, 2015). Outer membrane loops 1 and 2 of OmpP5 contribute to the binding of FH via unidentified aa residues.…”

Section: Inhibiting the Ap: Fh And Fhl-1mentioning

confidence: 99%

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Hijacking Complement Regulatory Proteins for Bacterial Immune Evasion

2016

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The human complement system plays an important role in the defense against invading pathogens, inflammation and homeostasis. Invading microbes, such as bacteria, directly activate the complement system resulting in the formation of chemoattractants and in effective labeling of the bacteria for phagocytosis. In addition, formation of the membrane attack complex is responsible for direct killing of Gram-negative bacteria. In turn, bacteria have evolved several ways to evade complement activation on their surface in order to be able to colonize and invade the human host. One important mechanism of bacterial escape is attraction of complement regulatory proteins to the microbial surface. These molecules are present in the human body for tight regulation of the complement system to prevent damage to host self-surfaces. Therefore, recruitment of complement regulatory proteins to the bacterial surface results in decreased complement activation on the microbial surface which favors bacterial survival. This review will discuss recent advances in understanding the binding of complement regulatory proteins to the bacterial surface at the molecular level. This includes, new insights that have become available concerning specific conserved motives on complement regulatory proteins that are favorable for microbial binding. Finally, complement evasion molecules are of high importance for vaccine development due to their dominant role in bacterial survival, high immunogenicity and homology as well as their presence on the bacterial surface. Here, the use of complement evasion molecules for vaccine development will be discussed.

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Section: Inhibiting the Ap: Fh And Fhl-1mentioning

confidence: 99%

Section: Inhibiting the Ap: Fh And Fhl-1mentioning

confidence: 99%

Hijacking Complement Regulatory Proteins for Bacterial Immune Evasion

2016

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“…In addition to its role as a commensal, NTHi is a major cause of respiratory tract infections in children such as acute otitis media (AOM), acute sinusitis, and pneumonia especially in developing countries (17). In addition, NTHi is implicated in chronic infections of the lower respiratory tract in adults, such as chronic obstructive pulmonary disease (COPD) and chronic bronchitis (18-22).…”

Section: Discussionmentioning

confidence: 99%

Immunization with Protein D from Non-Typeable Haemophilus influenzae (NTHi) Induced Cytokine Responses and Bioactive Antibody Production

Motlagh

Siadat

Abediankenari

et al. 2016

Jundishapur J Microbiol

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BackgroundOuter membrane protein D (PD) is a highly conserved and stable protein in the outer membrane of both encapsulated (typeable) and non-capsulated (non-typeable) strains of Haemophilus influenzae. As an immunogen, PD is a potential candidate vaccine against non-typeable H. influenzae (NTHi) strains.ObjectivesThe aim of this study was to determine the cytokine pattern and the opsonic antibody response in a BALB/c mouse model versus PD from NTHi as a vaccine candidate.MethodsProtein D was formulated with Freund’s and outer membrane vesicle (OMV) adjuvants and injected into experimental mice. Sera from all groups were collected. The bioactivity of the anti-PD antibody was determined by opsonophagocytic killing test. To evaluate the cytokine responses, the spleens were assembled, suspension of splenocytes was recalled with antigen, and culture supernatants were analyzed by ELISA for IL-4, IL-10, and IFN-γ cytokines.ResultsAnti-PD antibodies promoted phagocytosis of NTHi in both immunized mice groups (those administered PD + Freund’s and those administered PD + OMV adjuvants, 92.8% and 83.5%, respectively, compared to the control group). In addition, the concentrations of three cytokines were increased markedly in immunized mice.ConclusionsWe conclude that immunization with PD protects mice against NTHi. It is associated with improvements in both cellular and humoral immune responses and opsonic antibody activity.

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“…13,14 On the basis of the above reasoning, NTHi has been increasingly recognized as emerging pathogen. 9,15,16 An effective vaccine against NTHi is not currently available. The pathogenesis of NTHi, which lacks the polysaccharide capsule, is associated with multiple virulence factors such as lipooligosaccharide (LOS), adhesins, other several surface structures, IgA protease and possibly biofilm formation in chronic and recurrent respiratory tract infections.…”

mentioning

confidence: 99%

“…6 However, despite the efficacy of Hib conjugate vaccines, invasive disease caused by non-vaccine preventable H. influenzae strains continues to occur, although with reduced incidence, mainly sustained by nontypeable H. influenzae (NTHi) followed at great distance by other capsular types. 7,8,9 Considering non-invasive disease due to H. influenzae, the upper and lower respiratory tract infections have been associated almost exclusively with NTHi, which is now the most frequently isolated bacterial pathogens in otitis media and sinusitis in children. 2,10 An increasing role for NTHi has been recently documented in episodes of acute exacerbation in adults with chronic obstructive pulmonary disease (COPD).…”

mentioning

confidence: 99%