The Immunostimulatory Capacity of Nontypeable Haemophilus influenzae Lipooligosaccharide

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Gabrielle N. Gaultier
Kayla N. Colledanchise
Alaa Alhazmi
Marina Ulanova

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.

Keywords: Nontypeable Haemophilus influenzae, Lipooligosaccharide, THP-1 cells, innate immune responses

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Author Biography

Marina Ulanova, Department of Biology, Lakehead University, Thunder Bay, ON, Canada; Northern Ontario School of Medicine, Thunder Bay, ON, Canada

Professor Marina Ulanova, MD, PhD, Immunologist

Division of Medical Sciences

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