Institutional Repository of Lund University

This is an author produced version of a paper published in Trends in Microbiology. This paper has been peer-reviewed but does not include the final publisher proof-corrections or journal pagination. "Haemophilus influenzae and the complement system." Access to the published version may require journal subscription. Abstract The respiratory tract pathogen Haemophilus influenzae is responsible for a variety of infections in humans including septicemia, bronchitis, pneumonia, and acute otitis media. The pathogenesis of H. influenzae relies on its capacity to resist the human host defenses including the complement system, and thus H. influenzae has developed several efficient strategies to circumvent the complement attack. In addition to attracting specific host complement regulators directly to the bacterial surface, the capsule, lipooligosaccharides, and several outer membrane proteins contribute to resistance against the complement-mediated attacks and hence increased bacterial survival. Insights into the mechanisms of complement evasion of H. influenzae are very important for understanding the pathogenesis, for development of vaccines and for new therapies aimed for patients with, for example, chronic obstructive pulmonary disease. This review gives an overview of our current knowledge on the different mechanisms by which H. influenzae conquers the host complement attack. The respiratory pathogen Haemophilus influenzae H. influenzae is a Gram-negative human specific pathogen responsible for a variety of diseases, and can be divided into encapsulated strains and unencapsulated strains according to the presence of a polysaccharide capsule. The capsule is the major virulence factor of invasive H. influenzae strains, and the encapsulated strains belong to one of six serotypes (a to f), where type b (Hib; see Glossary) is the most virulent one. Invasive disease caused by Hib mainly affects infants and children, causing potentially life-threatening conditions such as meningitis, epiglottitis, and severe sepsis [1]. After introduction of the capsular polysaccharide conjugate vaccine against Hib in the early 1990s, the incidence of invasive disease caused by Hib has decreased substantially in the Western hemisphere [2]. Since the 3 Hib vaccines do not protect against other capsule types or unencapsulated H. influenzae strains, invasive infections caused by non-type b strains have increased in frequency recent years [3-6]. Another important issue is that the Hib vaccine to date is not commonly used in developing countries, making large populations susceptible to all types of H. influenzae infections. In contrast to encapsulated H. influenzae, non-typeable Haemophilus influenzae (NTHi) is a commensal of the respiratory tract particularly in children but also among adults …