The Immunostimulatory Capacity of Nontypeable Haemophilus influenzae Lipooligosaccharide

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.

Tolerance to Haemophilus influenzae infection in human epithelial cells: Insights from a primary cell-based model

“…The effectors controlling this were endothelin (EDN1), TGFB, the CCR5 chemokine receptor and two interleukins, IL-17 and IL-36A, that were also involved in the day1 response to NTHi infection ( S4 Fig ). However, a strong hypoxia-related signature was missing on day7 ( Fig 4 ), and several additional effectors that were upregulated on day1 were downregulated on day7 p.i., including IL-10, which has anti-inflammatory properties, BCL6 that has been linked to susceptibility to influenza A infection, VIP, a major neuropeptide present in lung tissues and the LXR/RXR regulator pair [ 37 – 41 ].…”

Continuous Microevolution Accelerates Disease Progression during Sequential Episodes of Infection

“…LOS is an important modulator of the host immune responses and provides protection from host innate immune effectors (Gaultier et al, 2017;Tong et al, 2001). Previous studies suggest that truncation of the LOS outer core prevents binding by IgM and reduces serum sensitivity (Jackson et al, 2019).…”

Tolerance toHaemophilus influenzaeinfection in human epithelial cells: insights from a primary cell-based model

“…The effectors controlling this were endothelin (EDN1), TGFB, the CCR5 chemokine receptor and two interleukins, IL17 and IL36A, that were also involved in the day1 response to NTHi infection (Figure S3). However, a strong hypoxia-related signature was missing on day7 (Figure 4), and several additional effectors that were upregulated on day1 were downregulated on day7 p.i., including IL10, which has anti-inflammatory properties, BCL6 that has been linked to susceptibility to influenza A infection, VIP, a major neuropeptide present in lung tissues and the LXR/RXR regulator pair [37][38][39][40][41] .…”