Non-typeable Haemophilus influenzae isolates vary in ability to survive in human plasma which correlates with binding of innate immune complement components
Author(s): ,
Stephanie Leung
Affiliations:
Public Health England
,
Stephen Thomas
Affiliations:
Public Health England
,
Stephen Taylor
Affiliations:
Public Health England
Andrew Gorringe
Affiliations:
Public Health England
PHE ePoster Library. Leung S. Mar 20, 2018; 205925; 12596
Stephanie Leung
Stephanie Leung
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Abstract
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Abstract Introduction: Non-typeable Haemophilus influenzae (NTHi) is a Gram-negative opportunistic bacterium colonising the human nasopharynx causing a range of mucosal infections including acute otitis media (AOM) and is frequently implicated with exacerbations in patients of chronic obstructive pulmonary disease (COPD). Rarely, NTHi can also cause invasive disease. Introduction of Haemophilus influenzae type B (Hib) vaccine led to a decline in invasive Hib cases; however NTHi-disease has steadily increased in infants, the elderly and immunocompromised people. Increasing resistance to antibiotics in many bacterial species suggests prevention of disease by vaccination may be more effective. The immune correlate of protection for Hib disease is bactericidal antibody and it is likely that antibody and complement-mediated killing will be required for NTHi. We have investigated survival of NTHi isolates in human plasma and the binding of various complement components.Methods and results: NTHi isolates (n=101) from AOM, CODP and invasive disease were provided by David Litt (Respiratory and Vaccine Preventable Bacteria Reference Unit, PHE), Derek Hood (MRC, Harwell) and Karl Staples (NCT01701869, University Hospital Southampton NHS Foundation Trust). Isolates were incubated in IgG-depleted human plasma and survival determined. Some strains were resistant to antibody-independent killing whilst others were highly sensitive. As the complement terminal pathway results in formation of membrane attack complex, binding of C5b-9 to surface of bacteria was determined using flow cytometry. There was an inverse correlation between survival and binding of C5b-9 on the bacterial surface (r=-0.68). Complement regulatory proteins, factor H and vitronectin, was also found to vary from high levels of binding to no binding.Conclusion: NTHi strains comprise a diverse group that range from highly sensitive to killing in human plasma to highly resistant. Binding of various complement components indicates that NTHi isolates may utilise different immune evasion mechanisms with no single dominant factor. Funding Grant in aid through PHE
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