Role of haemophilus influenzae lipooligosaccharide in the activation of innate and adaptive immunity
Master of Science
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A Gram negative human bacterial pathogen Haemophilus influenzae expresses a truncated endotoxin known as lipooligosaccharide (LOS). Recent studies on H. influenzae LOS have highlighted its structural and compositional implications on bacterial virulence; however, the role of LOS in the activation of innate and adaptive immunity is poorly understood. THP-1 monocytes were stimulated with either lipopolysaccharide (LPS) from E. coli or LOS compounds derived from Eagan, Rd, and Rd lie lips A H. influenzae strains. Cell surface expression of key antigen-presenting, co-stimulatory, and adhesion molecules, as well as gene expression of some cytokines and pattern recognition receptors were studied. Eagan and Rd LOS had a lower capacity to induce the expression of the pro-inflammatory molecules, ICAM-1, CD40, CD58, TNF-a, and IL-lp compared to LPS. In contrast, antigen presenting (HLA-ABC, HLA-DR) and co-stimulatory (CD86) molecules, and the pattern recognition receptor, NOD2, were similarly upregulated in response to LOS and LPS. LOS from a mutant Rd strain (Rd licllpsA) consistently induced higher expression of innate immune molecules than the wildtype LOS suggesting the importance of phosphorylcholine and/or oligosaccharide extension in cellular responses to LOS. An LOS compound with a strong ability to upregulate antigen-presenting and co-stimulatory molecules combined with a low proinflammatory activity may be considered as a vaccine candidate to immunize against H. influenzae.