Inflammatory Responses to Non-Typeable Haemophilus influenzae Clinical Isolates from Invasive and Non-Invasive Infections.

Abstract

Non-typeable Haemophilus influenzae (NTHi) is often asymptomatically carried in the upper airways but can cause a wide spectrum of disease conditions, from local respiratory tract infections to invasive disease such as sepsis or meningitis. The factors driving NTHi's transition from benign carriage to severe systemic disease remain poorly understood. It is unknown whether NTHi strains associated with invasive or non-invasive disease differ in their capacity to trigger inflammatory responses in innate immune cells. To address this question, we have used an in vitro infection model of human THP-1 cells differentiated to macrophages. To evaluate inflammatory responses, we studied the expression of 3 prototypic pro-inflammatory molecules, ICAM-1, TNF-α, and IL-1β. The role of lipooligosaccharide in triggering inflammatory responses was assessed using inhibition of Toll-like receptor 4 signaling. Our experiments demonstrated that NTHi strains isolated from cases of invasive and non-invasive infections were similarly able to induce strong activations of macrophage pro-inflammatory responses. Our findings support the hypothesis that the development of invasive versus non-invasive NTHi disease may be more significantly influenced by the adaptive immune response than the innate immune response.