Abstract
Background:We have recently found that lipooligosaccharide (LOS) isolated from encapsulated strains of Haemophilus influenzae (H. influenzae) has strong adjuvant, but diminished pro-inflammatory ability as compared to Escherichia coli lipopolysaccharide (LPS). In this study, we aimed to determine the immunostimulatory capacity of nontypeable/ non-encapsulated H. influenzae (NTHi) LOS by comparing the effect of killed bacteria with LOS isolated from the same strain.Methods:Following stimulation of human monocytic THP-1 cells with killed NTHi strain 375, or with the corresponding amount of LOS, we studied the protein and gene expression of immunostimulatory and antigen-presenting molecules, cytokines, and innate immune receptors.Results:Stimulation with LOS resulted in lower expression of adhesion (CD54, CD58) as well as costimulatory molecules (CD40, CD86), but in higher expression of antigen-presenting molecules (HLA-DR and HLA-ABC) compared to killed NTHi, whereas killed bacteria induced higher release of both TNF-α and IL-10. The results indicate that while LOS of NTHi has decreased capacity to induce pro-inflammatory responses compared to E. coli LPS or killed NTHi, this LOS has the potential to facilitate antigen presentation.Conclusions:Considering the important role of NTHi as a respiratory pathogen, and its currently increasing significance in the etiology of invasive infections, LOS deserves further attention as a vaccine antigen, which also has potent adjuvant properties.
Highlights
Nonencapsulated, or nontypeable Haemophilus influenzae (NTHi) is an important gram-negative human pathogen, which frequently colonizes the upper respiratory tract and is a common cause of local infections, such as sinusitis, pediatric otitis media, or exacerbations of chronic obstructive pulmonary disease (COPD) [1, 2]
The results indicate that while LOS of non-encapsulated H. influenzae (NTHi) has decreased capacity to induce pro-inflammatory responses compared to E. coli LPS or killed NTHi, this LOS has the potential to facilitate antigen presentation
Several H. influenzae antigenic compounds have been considered as potential NTHi-vaccine candidates, and some have been tested in animal models; none went beyond phase I clinical trials [7,8,9,10,11,12]
Summary
Nonencapsulated, or nontypeable Haemophilus influenzae (NTHi) is an important gram-negative human pathogen, which frequently colonizes the upper respiratory tract and is a common cause of local infections, such as sinusitis, pediatric otitis media, or exacerbations of chronic obstructive pulmonary disease (COPD) [1, 2]. Lipooligosaccharide (LOS) is a major virulence factor of H. influenzae that is responsible for inflammatory responses associated with this infection [13]. This LOS is similar to one of the most studied endotoxin molecules, the lipopolysaccharide (LPS) of gram-negative bacteria. The structure of LPS consists of 3 covalently -linked components: lipid A embedded into the outer membrane, the oligosaccharide core, and the polysaccharide or O-antigen that covers the surface of the bacteria [14], and LPS activates the innate immune response once bound to the cellular receptor CD14, myeloid differentiation protein 2 (MD-2), and Toll-like receptor 4 (TLR4) [15]. We aimed to determine the immunostimulatory capacity of nontypeable/ non-encapsulated H. influenzae (NTHi) LOS by comparing the effect of killed bacteria with LOS isolated from the same strain
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